Candidate rejuvenating factor GDF11 and tissue fibrosis: friend or foe?
Jazyk angličtina Země Švýcarsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem, přehledy
PubMed
33025411
PubMed Central
PMC7732895
DOI
10.1007/s11357-020-00279-w
PII: 10.1007/s11357-020-00279-w
Knihovny.cz E-zdroje
- Klíčová slova
- BMP11, Fibrosis, GDF11, Growth differentiation factor 11,
- MeSH
- fibróza MeSH
- kostní morfogenetické proteiny * MeSH
- myši MeSH
- růstové diferenciační faktory * MeSH
- stárnutí MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- Gdf11 protein, mouse MeSH Prohlížeč
- kostní morfogenetické proteiny * MeSH
- růstové diferenciační faktory * MeSH
Growth differentiation factor 11 (GDF11 or bone morphogenetic protein 11, BMP11) belongs to the transforming growth factor-β superfamily and is closely related to other family member-myostatin (also known as GDF8). GDF11 was firstly identified in 2004 due to its ability to rejuvenate the function of multiple organs in old mice. However, in the past few years, the heralded rejuvenating effects of GDF11 have been seriously questioned by many studies that do not support the idea that restoring levels of GDF11 in aging improves overall organ structure and function. Moreover, with increasing controversies, several other studies described the involvement of GDF11 in fibrotic processes in various organ setups. This review paper focuses on the GDF11 and its pro- or anti-fibrotic actions in major organs and tissues, with the goal to summarize our knowledge on its emerging role in regulating the progression of fibrosis in different pathological conditions, and to guide upcoming research efforts.
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Jun J-I, Lau LF. Resolution of organ fibrosis. J Clin Invest. 128:97–107. PubMed PMC
Rosenbloom J. Narrative review: fibrotic diseases: cellular and molecular mechanisms and novel therapies. Ann Intern Med. 2010;152:159. PubMed
Wynn T. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214:199–210. PubMed PMC
Wynn TA. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol. 2004;4:583–594. PubMed PMC
Kong P, Christia P, Frangogiannis NG. The pathogenesis of cardiac fibrosis. Cell Mol Life Sci. 2014;71:549–574. PubMed PMC
Thannickal VJ, Toews GB, White ES, Lynch JP, Martinez FJ. Mechanisms of pulmonary fibrosis. Annu Rev Med. 2004;55:395–417. PubMed
Tsukada S, Parsons CJ, Rippe RA. Mechanisms of liver fibrosis. Clin Chim Acta. 2006;364:33–60. PubMed
Zeisberg M, Kalluri R. Cellular mechanisms of tissue fibrosis. 1. Common and organ-specific mechanisms associated with tissue fibrosis. Am J Phys Cell Phys. 2013;304:C216–C225. PubMed PMC
Gabbiani G. The myofibroblast in wound healing and fibrocontractive diseases. J Pathol. 2003;200:500–503. PubMed
Karsdal MA, Manon-Jensen T, Genovese F, Kristensen JH, Nielsen MJ, Sand JMB, Hansen N-UB, Bay-Jensen A-C, Bager CL, Krag A, Blanchard A, Krarup H, Leeming DJ, et al. Novel insights into the function and dynamics of extracellular matrix in liver fibrosis. Am J Physiol-Gastrointest Liver Physiol Am Physiol Soc. 2015;308:G807–G830. PubMed PMC
Rosenbloom J, Mendoza FA, Jimenez SA. Strategies for anti-fibrotic therapies. Biochim Biophys Acta (BBA) - Mol Basis Dis. 2013;1832:1088–1103. PubMed
Thannickal VJ, Henke CA, Horowitz JC, Noble PW, Roman J, Sime PJ, Zhou Y, Wells RG, White ES, Tschumperlin DJ. Matrix biology of idiopathic pulmonary fibrosis: a workshop report of the National Heart, Lung, and Blood Institute. Am J Pathol. 2014;184:1643–1651. PubMed PMC
Kendall RT, Feghali-Bostwick CA. Fibroblasts in fibrosis: novel roles and mediators. Front Pharmacol. 2014;5:123. doi: 10.3389/fphar.2014.00123. PubMed DOI PMC
Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453:314–321. PubMed
Stramer BM, Mori R, Martin P. The inflammation-fibrosis link? A Jekyll and Hyde role for blood cells during wound repair. J Invest Dermatol. 2007;127:1009–1017. PubMed
Anders H-J, Muruve DA. The inflammasomes in kidney disease. J Am Soc Nephrol JASN. 2011;22:1007–1018. PubMed
Koyama Y, Brenner DA. Liver inflammation and fibrosis. J Clin Invest. 127:55–64. PubMed PMC
Sanjuan MA, Dillon CP, Tait SWG, Moshiach S, Dorsey F, Connell S, Komatsu M, Tanaka K, Cleveland JL, Withoff S, Green DR. Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature. 2007;450:1253–1257. PubMed
Harris HE, Raucci A. Alarmin(g) news about danger: workshop on innate danger signals and HMGB1. EMBO Rep. 2006;7:774–778. PubMed PMC
Oppenheim JJ, Yang D. Alarmins: chemotactic activators of immune responses. Curr Opin Immunol. 2005;17:359–365. PubMed
Rittirsch D, Flierl MA, Ward PA. Harmful molecular mechanisms in sepsis. Nat Rev Immunol. 2008;8:776–787. PubMed PMC
Broekelmann TJ, Limper AH, Colby TV, McDonald JA. Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci U S A. 1991;88:6642–6646. PubMed PMC
Nagaoka I, Trapnell BC, Crystal RG. Upregulation of platelet-derived growth factor-A and -B gene expression in alveolar macrophages of individuals with idiopathic pulmonary fibrosis. J Clin Invest. 1990;85:2023–2027. PubMed PMC
Varga J, Jimenez SA. Stimulation of normal human fibroblast collagen production and processing by transforming growth factor-β. Biochem Biophys Res Commun. 1986;138:974–980. PubMed
Sandbo N, Dulin N. The actin cytoskeleton in myofibroblast differentiation: ultrastructure defining form and driving function. Transl Res. 2011;158:181–196. PubMed PMC
Desmoulière A. Factors influencing myofibroblast differentiation during wound healing and fibrosis. Cell Biol Int. 1995;19:471–476. PubMed
Distler JHW, Györfi A-H, Ramanujam M, Whitfield ML, Königshoff M, Lafyatis R. Shared and distinct mechanisms of fibrosis. Nat Rev Rheumatol Nat. 2019;15:705–730. PubMed
Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat M-L, Gabbiani G. The myofibroblast: one function, multiple origins. Am J Pathol. 2007;170:1807–1816. PubMed PMC
McAnulty RJ. Fibroblasts and myofibroblasts: their source, function and role in disease. Int J Biochem Cell Biol. 2007;39:666–671. PubMed
Chen L-J, Ye H, Zhang Q, Li F-Z, Song L-J, Yang J, Mu Q, Rao S-S, Cai P-C, Xiang F, Zhang J-C, Su Y, Xin J-B, et al. Bleomycin induced epithelial-mesenchymal transition (EMT) in pleural mesothelial cells. Toxicol Appl Pharmacol. 2015;283:75–82. PubMed
Humphreys BD, Lin S-L, Kobayashi A, Hudson TE, Nowlin BT, Bonventre JV, Valerius MT, McMahon AP, Duffield JS. Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol. 2010;176:85–97. PubMed PMC
Inoue T, Okada H, Takenaka T, Watanabe Y, Suzuki H. A case report suggesting the occurrence of epithelial-mesenchymal transition in obstructive nephropathy. Clin Exp Nephrol. 2009;13:385–388. PubMed
Mubarak KK, Montes-Worboys A, Regev D, Nasreen N, Mohammed KA, Faruqi I, Hensel E, Baz MA, Akindipe OA, Fernandez-Bussy S, Nathan SD, Antony VB. Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis. Eur Respir J. 2012;39:133–140. PubMed
Omenetti A, Porrello A, Jung Y, Yang L, Popov Y, Choi SS, Witek RP, Alpini G, Venter J, Vandongen HM, Syn W-K, Baroni GS, Benedetti A, et al. Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans. J Clin Invest. 2008;118:3331–3342. PubMed PMC
Abraham DJ, Eckes B, Rajkumar V, Krieg T. New developments in fibroblast and myofibroblast biology: implications for fibrosis and scleroderma. Curr Rheumatol Rep. 2007;9:136–143. PubMed
Gilbane AJ, Denton CP, Holmes AM. Scleroderma pathogenesis: a pivotal role for fibroblasts as effector cells. Arthritis Res Ther. 2013;15:215. PubMed PMC
Noble PW, Barkauskas CE, Jiang D. Pulmonary fibrosis: patterns and perpetrators. J Clin Invest. 2012;122:2756–2762. PubMed PMC
Wright JL, Tazelaar HD, Churg A. Fibrosis with emphysema. Histopathology. 2011;58:517–524. PubMed
Bocchino M, Agnese S, Fagone E, Svegliati S, Grieco D, Vancheri C, Gabrielli A, Sanduzzi A, Avvedimento EV. Reactive oxygen species are required for maintenance and differentiation of primary lung fibroblasts in idiopathic pulmonary fibrosis. PLoS One. 2010;5:e14003. PubMed PMC
Schaberg T, Rau M, Stephan H, Lode H. Increased number of alveolar macrophages expressing surface molecules of the CD11/CD18 family in sarcoidosis and idiopathic pulmonary fibrosis is related to the production of superoxide anions by these cells. Am Rev Respir Dis. 1993;147:1507–1513. PubMed
Ye Q, Dalavanga Y, Poulakis N, Sixt SU, Guzman J, Costabel U. Decreased expression of haem oxygenase-1 by alveolar macrophages in idiopathic pulmonary fibrosis. Eur Respir J. 2008;31:1030–1036. PubMed
Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A. Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med Camb Mass. 1994;1:71–81. PubMed PMC
Hashimoto N, Jin H, Liu T, Chensue SW, Phan SH. Bone marrow-derived progenitor cells in pulmonary fibrosis. J Clin Invest. 2004;113:243–252. PubMed PMC
Postlethwaite AE, Shigemitsu H, Kanangat S. Cellular origins of fibroblasts: possible implications for organ fibrosis in systemic sclerosis. Curr Opin Rheumatol. 2004;16:733–738. PubMed
Willis BC, Liebler JM, Luby-Phelps K, Nicholson AG, Crandall ED, du Bois RM, Borok Z. Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-β1. Am J Pathol. 2005;166:1321–1332. PubMed PMC
Kim KK, Kugler MC, Wolters PJ, Robillard L, Galvez MG, Brumwell AN, Sheppard D, Chapman HA. Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci U S A. 2006;103:13180–13185. PubMed PMC
Tanjore H, Xu XC, Polosukhin VV, Degryse AL, Li B, Han W, Sherrill TP, Plieth D, Neilson EG, Blackwell TS, Lawson WE. Contribution of epithelial-derived fibroblasts to bleomycin-induced lung fibrosis. Am J Respir Crit Care Med. 2009;180:657–665. PubMed PMC
Fintha A, Gasparics Á, Rosivall L, Sebe A. Therapeutic targeting of fibrotic epithelial-mesenchymal transition–an outstanding challenge. Front Pharmacol. 2019;10:388. doi: 10.3389/fphar.2019.00388. PubMed DOI PMC
Rock JR, Barkauskas CE, Cronce MJ, Xue Y, Harris JR, Liang J, Noble PW, Hogan BLM. Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition. Proc Natl Acad Sci U S A. 2011;108:E1475–E1483. PubMed PMC
Rout-Pitt N, Farrow N, Parsons D, Donnelley M. Epithelial mesenchymal transition (EMT): a universal process in lung diseases with implications for cystic fibrosis pathophysiology. Respir Res. 2018;19:136. PubMed PMC
Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest. 2002;110:341–350. PubMed PMC
Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest Am Soc Clin Invest. 2003;112:1776–1784. PubMed PMC
Fragiadaki M, Mason RM. Epithelial-mesenchymal transition in renal fibrosis–evidence for and against. Int J Exp Pathol. 2011;92:143–150. PubMed PMC
Kisseleva T, Brenner DA. Fibrogenesis of parenchymal organs. Proc Am Thorac Soc Am Thor Soc – PATS. 2008;5:338–342. PubMed PMC
Duffield JS, Humphreys BD. Origin of new cells in the adult kidney: results from genetic labeling techniques. Kidney Int. 2011;79:494–501. PubMed
Koesters R, Kaissling B, Lehir M, Picard N, Theilig F, Gebhardt R, Glick AB, Hähnel B, Hosser H, Gröne H-J, Kriz W. Tubular overexpression of transforming growth factor-beta1 induces autophagy and fibrosis but not mesenchymal transition of renal epithelial cells. Am J Pathol. 2010;177:632–643. PubMed PMC
Sato Y, Yanagita M. Resident fibroblasts in the kidney: a major driver of fibrosis and inflammation. Inflamm Regen. 2017;37:17. PubMed PMC
Humphreys BD. Mechanisms of renal fibrosis. Annu Rev Physiol. 2018;80:309–326. PubMed
Grande MT, Sánchez-Laorden B, López-Blau C, De Frutos CA, Boutet A, Arévalo M, Rowe RG, Weiss SJ, López-Novoa JM, Nieto MA. Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease. Nat Med. 2015;21:989–997. PubMed
Hertig A, Anglicheau D, Verine J, Pallet N, Touzot M, Ancel P-Y, Mesnard L, Brousse N, Baugey E, Glotz D, Legendre C, Rondeau E, Xu-Dubois Y-C. Early epithelial phenotypic changes predict graft fibrosis. J Am Soc Nephrol JASN. 2008;19:1584–1591. PubMed PMC
Huang S, Susztak K. Epithelial plasticity versus EMT in kidney fibrosis. Trends Mol Med. 2016;22:4–6. PubMed PMC
Asada N, Takase M, Nakamura J, Oguchi A, Asada M, Suzuki N, Yamamura K, Nagoshi N, Shibata S, Rao TN, Fehling HJ, Fukatsu A, Minegishi N, et al. Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice. J Clin Invest. 2011;121:3981–3990. PubMed PMC
Paliege A, Rosenberger C, Bondke A, Sciesielski L, Shina A, Heyman SN, Flippin LA, Arend M, Klaus SJ, Bachmann S. Hypoxia-inducible factor-2alpha-expressing interstitial fibroblasts are the only renal cells that express erythropoietin under hypoxia-inducible factor stabilization. Kidney Int. 2010;77:312–318. PubMed
Zhang Y, Zhu X, Huang X, Wei X, Zhao D, Jiang L, Zhao X, Du Y. Advances in understanding the effects of erythropoietin on renal fibrosis. Front Med. 2020;7:47. doi: 10.3389/fmed.2020.00047. PubMed DOI PMC
Fan X, Gaur U, Sun L, Yang D, Yang M. The growth differentiation factor 11 (GDF11) and myostatin (MSTN) in tissue specific aging. Mech Ageing Dev. 2017;164:108–112. PubMed
Biernacka A, Dobaczewski M, Frangogiannis NG. TGF-β signaling in fibrosis. Growth Factors Chur Switz. 2011;29:196–202. PubMed PMC
Graham-Brown MPM, Patel AS, Stensel DJ, March DS, Marsh A-M, McAdam J, McCann GP, Burton JO. Imaging of myocardial fibrosis in patients with end-stage renal disease: current limitations and future possibilities. Biomed Res Int 2017:e5453606. https:/doi.org/10.1155/2017/5453606. https://www.hindawi.com/journals/bmri/2017/5453606/ PubMed PMC
Krenning G, Zeisberg EM, Kalluri R. The origin of fibroblasts and mechanism of cardiac fibrosis. J Cell Physiol. 2010;225:631–637. PubMed PMC
Rog-Zielinska EA, Norris RA, Kohl P, Markwald R. The living scar--cardiac fibroblasts and the injured heart. Trends Mol Med. 2016;22:99–114. PubMed PMC
Forte E, Furtado MB, Rosenthal N. The interstitium in cardiac repair: role of the immune–stromal cell interplay. Nat Rev Cardiol. 2018;15:601–616. PubMed
Ma Z-G, Yuan Y-P, Wu H-M, Zhang X, Tang Q-Z. Cardiac fibrosis: new insights into the pathogenesis. Int J Biol Sci. 2018;14:1645–1657. PubMed PMC
Pinto AR, Ilinykh A, Ivey MJ, Kuwabara JT, D’Antoni ML, Debuque R, Chandran A, Wang L, Arora K, Rosenthal N, Tallquist MD. Revisiting cardiac cellular composition. Circ Res. 2016;118:400–409. PubMed PMC
Chen WCW, Baily JE, Corselli M, Díaz ME, Sun B, Xiang G, Gray GA, Huard J, Péault B. Human myocardial pericytes: multipotent mesodermal precursors exhibiting cardiac specificity. Stem Cells Dayt Ohio. 2015;33:557–573. PubMed PMC
Dulauroy S, Di Carlo SE, Langa F, Eberl G, Peduto L. Lineage tracing and genetic ablation of ADAM12(+) perivascular cells identify a major source of profibrotic cells during acute tissue injury. Nat Med. 2012;18:1262–1270. PubMed
Chang Y, Li H, Guo Z. Mesenchymal stem cell-like properties in fibroblasts. Cell Physiol Biochem Int J Exp Cell PhysiolBiochem Pharmacol. 2014;34:703–714. PubMed
Furtado MB, Nim HT, Boyd SE, Rosenthal NA. View from the heart: cardiac fibroblasts in development, scarring and regeneration. Development. 2016;143:387–397. PubMed
Liu Y, Hu Z-F, Liao H-H, Liu W, Liu J, Ma Z-G, Wu Q-Q, Xu M, Zhang N, Zhang Y, Bian Z-Y, Tang Q-Z. Toll-like receptor 5 deficiency attenuates interstitial cardiac fibrosis and dysfunction induced by pressure overload by inhibiting inflammation and the endothelial-mesenchymal transition. Biochim Biophys Acta. 2015;1852:2456–2466. PubMed
Ranjan P, Kumari R, Verma SK. Cardiac fibroblasts and cardiac fibrosis: precise role of exosomes. Front Cell Dev Biol. 2019;7:318. doi: 10.3389/fcell.2019.00318. PubMed DOI PMC
Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, Chandraker A, Yuan X, Pu WT, Roberts AB, Neilson EG, Sayegh MH, Izumo S, et al. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med. 2007;13:952–961. PubMed
Fang M, Xiang F-L, Braitsch CM, Yutzey KE. Epicardium-derived fibroblasts in heart development and disease. J Mol Cell Cardiol. 2016;91:23–27. PubMed PMC
Ruiz-Villalba A, Simón AM, Pogontke C, Castillo MI, Abizanda G, Pelacho B, Sánchez-Domínguez R, Segovia JC, Prósper F, Pérez-Pomares JM. Interacting resident epicardium-derived fibroblasts and recruited bone marrow cells form myocardial infarction scar. J Am Coll Cardiol. 2015;65:2057–2066. PubMed
Bersini S, Gilardi M, Mora M, Krol S, Arrigoni C, Candrian C, Zanotti S, Moretti M. Tackling muscle fibrosis: from molecular mechanisms to next generation engineered models to predict drug delivery. Adv Drug Deliv Rev. 2018;129:64–77. PubMed
Mahdy MAA. Skeletal muscle fibrosis: an overview. Cell Tissue Res. 2019;375:575–588. PubMed
Goodpaster BH, Thaete FL, Kelley DE. Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus. Am J Clin Nutr. 2000;71:885–892. PubMed
Greco AV, Mingrone G, Giancaterini A, Manco M, Morroni M, Cinti S, Granzotto M, Vettor R, Camastra S, Ferrannini E. Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion. Diabetes. 2002;51:144–151. PubMed
Järvinen TA, Kääriäinen M, Järvinen M, Kalimo H. Muscle strain injuries. Curr Opin Rheumatol. 2000;12:155–161. PubMed
Serrano AL, Muñoz-Cánoves P. Regulation and dysregulation of fibrosis in skeletal muscle. Exp Cell Res. 2010;316:3050–3058. PubMed
Delaney K, Kasprzycka P, Ciemerych MA, Zimowska M. The role of TGF-β1 during skeletal muscle regeneration. Cell Biol Int. 2017;41:706–715. PubMed
Järvinen TAH, Józsa L, Kannus P, Järvinen TLN, Järvinen M. Organization and distribution of intramuscular connective tissue in normal and immobilized skeletal muscles. An immunohistochemical, polarization and scanning electron microscopic study. J Muscle Res Cell Motil. 2002;23:245–254. PubMed
Murphy S, Ohlendieck K. The biochemical and mass spectrometric profiling of the dystrophin complexome from skeletal muscle. Comput Struct Biotechnol J. 2015;14:20–7. doi: 10.1016/j.csbj.2015.11.002. PubMed DOI PMC
Prazeres PHDM, Turquetti AOM, Azevedo PO, Barreto RSN, Miglino MA, Mintz A, Delbono O, Birbrair A. Perivascular cell αv integrins as a target to treat skeletal muscle fibrosis. Int J Biochem Cell Biol. 2018;99:109–113. PubMed PMC
Perandini LA, Chimin P, Lutkemeyer D d S, Câmara NOS. Chronic inflammation in skeletal muscle impairs satellite cells function during regeneration: can physical exercise restore the satellite cell niche? FEBS J. 2018;285:1973–1984. PubMed
Tidball JG. Inflammatory processes in muscle injury and repair. Am J Phys Regul Integr Comp Phys. 2005;288:R345–R353. PubMed
Tidball JG, Welc SS. Macrophage-derived IGF-1 is a potent coordinator of myogenesis and inflammation in regenerating muscle. Mol Ther. 2015;23:1134–1135. PubMed PMC
Braga TT, Agudelo JSH, Camara NOS. Macrophages during the fibrotic process: M2 as friend and foe. Front Immunol. 2015;6:602. doi: 10.3389/fimmu.2015.00602. PubMed DOI PMC
Lemos DR, Babaeijandaghi F, Low M, Chang C-K, Lee ST, Fiore D, Zhang R-H, Natarajan A, Nedospasov SA, Rossi FMV. Nilotinib reduces muscle fibrosis in chronic muscle injury by promoting TNF-mediated apoptosis of fibro/adipogenic progenitors. Nat Med. 2015;21:786–794. PubMed
Murray IR, Gonzalez ZN, Baily J, Dobie R, Wallace RJ, Mackinnon AC, Smith JR, Greenhalgh SN, Thompson AI, Conroy KP, Griggs DW, Ruminski PG, Gray GA, et al. αv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis. Nat Commun. 2017;8:1118. PubMed PMC
Cholok D, Lee E, Lisiecki J, Agarwal S, Loder S, Ranganathan K, Qureshi AT, Davis TA, Levi B. Traumatic muscle fibrosis: from pathway to prevention. J Trauma Acute Care Surg. 2017;82:174–184. PubMed PMC
Ciciliot S, Schiaffino S. Regeneration of mammalian skeletal muscle. Basic mechanisms and clinical implications. Curr Pharm Des. 2010;16:906–914. PubMed
Ding J, Tredget EE. Cellular and molecular mechanism of dermal fibrosis following burn injury, and exploration of therapeutic approaches. J Aesthetic Reconstr Surg. 2016;1:3. doi: 10.4172/2472-1905.10003. DOI
Nejati R, Kovacic D, Slominski A. Neuro-immune-endocrine functions of the skin: an overview. Expert Rev Dermatol. 2013;8:581–583. PubMed PMC
Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res Eur Chir Forsch Rech Chir Eur. 2012;49:35–43. PubMed
Glim JE, van Egmond M, Niessen FB, Everts V, Beelen RHJ. Detrimental dermal wound healing: what can we learn from the oral mucosa? Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 2013;21:648–660. PubMed
Karppinen S-M, Heljasvaara R, Gullberg D, Tasanen K, Pihlajaniemi T. Toward understanding scarless skin wound healing and pathological scarring. F1000Research. 2019;8:787. PubMed PMC
Soehnlein O, Lindbom L. Phagocyte partnership during the onset and resolution of inflammation. Nat Rev Immunol. 2010;10:427–439. PubMed
Ridiandries A, Tan JTM, Bursill CA. The role of chemokines in wound healing. Int J Mol Sci. 2018;19(10):3217. doi: 10.3390/ijms19103217. PubMed DOI PMC
Su Y, Richmond A. Chemokine regulation of neutrophil infiltration of skin wounds. Adv Wound Care. 2015;4:631–640. PubMed PMC
Driskell RR, Lichtenberger BM, Hoste E, Kretzschmar K, Simons BD, Charalambous M, Ferron SR, Herault Y, Pavlovic G, Ferguson-Smith AC, Watt FM. Distinct fibroblast lineages determine dermal architecture in skin development and repair. Nature. 2013;504:277–281. PubMed PMC
Driskell RR, Watt FM. Understanding fibroblast heterogeneity in the skin. Trends Cell Biol. 2015;25:92–99. PubMed
Hinz B. The role of myofibroblasts in wound healing. Curr Res Transl Med. 2016;64:171–177. PubMed
Ng CP, Hinz B, Swartz MA. Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro. J Cell Sci. 2005;118:4731–4739. PubMed
Vallée A, Lecarpentier Y. TGF-β in fibrosis by acting as a conductor for contractile properties of myofibroblasts. Cell Biosci. 2019;9:98. PubMed PMC
Jagadeesan J, Bayat A. Transforming growth factor beta (TGFβ) and keloid disease. Int J Surg. 2007;5:278–285. PubMed
Cañedo-Dorantes L, Cañedo-Ayala M. Skin Acute Wound healing: a comprehensive review. Int J Inflam. 2019:e3706315. 10.1155/2019/3706315. https://www.hindawi.com/journals/iji/2019/3706315/ PubMed PMC
Marshall CD, Hu MS, Leavitt T, Barnes LA, Lorenz HP, Longaker MT. Cutaneous scarring: basic science, current treatments, and future directions. Adv Wound Care. 2018;7:29–45. PubMed PMC
Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med Camb Mass. 2011;17:113–125. PubMed PMC
Lichtman MK, Otero-Vinas M, Falanga V. Transforming growth factor beta (TGF-β) isoforms in wound healing and fibrosis. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 2016;24:215–222. PubMed
Ogawa R, Akaishi S, Kuribayashi S, Miyashita T. Keloids and hypertrophic scars can now be cured completely: recent progress in our understanding of the pathogenesis of keloids and hypertrophic scars and the most promising current therapeutic strategy. J Nippon Med Sch. 2016;83:46–53. PubMed
Khansa I, Harrison B, Janis JE. Evidence-Based scar management: how to improve results with technique and technology. Plast Reconstr Surg. 2016;138:165S–178S. PubMed
Luong VH, Chino T, Oyama N, Matsushita T, Sasaki Y, Ogura D, Niwa S, Biswas T, Hamasaki A, Fujita M, Okamoto Y, Otsuka M, Ihn H, et al. Blockade of TGF-β/Smad signaling by the small compound HPH-15 ameliorates experimental skin fibrosis. Arthritis Res Ther. 2018;20:46. PubMed PMC
Walton KL, Johnson KE, Harrison CA. Targeting TGF-β Mediated SMAD signaling for the prevention of fibrosis. Front Pharmacol. 2017;8:461. doi: 10.3389/fphar.2017.00461. PubMed DOI PMC
Crafts TD, Jensen AR, Blocher-Smith EC, Markel TA. Vascular endothelial growth factor: therapeutic possibilities and challenges for the treatment of ischemia. Cytokine. 2015;71:385–393. PubMed
Zubair M, Ahmad J. Role of growth factors and cytokines in diabetic foot ulcer healing: a detailed review. Rev Endocr Metab Disord. 2019;20:207–217. PubMed
Fallowfield JA, Kendall TJ, Iredale JP. Reversal of fibrosis: no longer a pipe dream? Clin Liver Dis. 2006;10:481–497. PubMed
Farci P, Roskams T, Chessa L, Peddis G, Mazzoleni AP, Scioscia R, Serra G, Lai ME, Loy M, Caruso L, DeSmet V, Purcell RH, Balestrieri A. Long-term benefit of interferon α therapy of chronic hepatitis D: regression of advanced hepatic fibrosis. Gastroenterology. 2004;126:1740–1749. PubMed
Ismail MH, Pinzani M. Reversal of liver fibrosis. Saudi J Gastroenterol. 2009;15:72. PubMed PMC
Cordero-Espinoza L, Huch M. The balancing act of the liver: tissue regeneration versus fibrosis. J Clin Invest Am Soc Clin Invest. 2018;128:85–96. PubMed PMC
Ahmad A, Ahmad R. Understanding the mechanism of hepatic fibrosis and potential therapeutic approaches. Saudi J Gastroenterol Off J Saudi Gastroenterol Assoc. 2012;18:155–167. PubMed PMC
Weiskirchen R, Weiskirchen S, Tacke F. Recent advances in understanding liver fibrosis: bridging basic science and individualized treatment concepts. F.F1000Res. 20187:F1000 Faculty Rev-921. 10.12688/f1000research.14841.1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024236/ PubMed PMC
Karlmark KR, Weiskirchen R, Zimmermann HW, Gassler N, Ginhoux F, Weber C, Merad M, Luedde T, Trautwein C, Tacke F. Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatol Baltim Md. 2009;50:261–274. PubMed
Meijer C, Wiezer MJ, Diehl AM, Schouten HJ, Schouten HJ, Meijer S, van Rooijen N, van Lambalgen AA, Dijkstra CD, van Leeuwen PA. Kupffer cell depletion by CI2MDP-liposomes alters hepatic cytokine expression and delays liver regeneration after partial hepatectomy. Liver. 2000;20:66–77. PubMed
Li Y, Lua I, French SW, Asahina K. Role of TGF-β signaling in differentiation of mesothelial cells to vitamin A-poor hepatic stellate cells in liver fibrosis. Am J Physiol Gastrointest Liver Physiol. 2016;310:G262–G272. PubMed PMC
Yin C, Evason KJ, Asahina K, Stainier DYR. Hepatic stellate cells in liver development, regeneration, and cancer. J Clin Invest. 2013;123:1902–1910. PubMed PMC
Carpino G, Renzi A, Franchitto A, Cardinale V, Onori P, Reid L, Alvaro D, Gaudio E. Stem/progenitor cell niches involved in hepatic and biliary regeneration. Stem Cells Int. 2016;2016:3658013. doi: 10.1155/2016/3658013. PubMed DOI PMC
Köhn-Gaone J, Gogoi-Tiwari J, Ramm GA, Olynyk JK, Tirnitz-Parker JEE. The role of liver progenitor cells during liver regeneration, fibrogenesis, and carcinogenesis. Am J Physiol Gastrointest Liver Physiol. 2016;310:G143–G154. PubMed
Blachier M, Leleu H, Peck-Radosavljevic M, Valla D-C, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013;58:593–608. PubMed
Stål P. Liver fibrosis in non-alcoholic fatty liver disease-diagnostic challenge with prognostic significance. World J Gastroenterol: WJG. 2015;21:11077–11087. PubMed PMC
Li S-N, Wu J-F. TGF-β/SMAD signaling regulation of mesenchymal stem cells in adipocyte commitment. Stem Cell Res Ther. 2020;11(1):41. doi: 10.1186/s13287-020-1552-y. PubMed DOI PMC
Morikawa M, Derynck R, Miyazono K. TGF-β and the TGF-β family: context-dependent roles in cell and tissue physiology. Cold Spring Harb Perspect Biol. 2016;8(5):a021873. doi: 10.1101/cshperspect.a021873. PubMed DOI PMC
Wang RN, Green J, Wang Z, Deng Y, Qiao M, Peabody M, Zhang Q, Ye J, Yan Z, Denduluri S, Idowu O, Li M, Shen C, et al. Bone morphogenetic protein (BMP) signaling in development and human diseases. Genes Dis. 2014;1:87–105. PubMed PMC
Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 1983;258:7155–7160. PubMed
Roberts AB, Anzano MA, Lamb LC, Smith JM, Sporn MB. New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues. Proc Natl Acad Sci U S A. 1981;78:5339–5343. PubMed PMC
Massagué J, Seoane J, Wotton D. Smad transcription factors. Genes Dev. 2005;19:2783–2810. PubMed
Katagiri T, Watabe T. Bone morphogenetic proteins. Cold Spring Harb Perspect Biol. 2016;8:a021899. PubMed PMC
Ramirez H, Patel SB, Pastar I. The role of TGFβ signaling in wound epithelialization. Adv Wound Care. 2014;3:482–491. PubMed PMC
Akhurst RJ, Derynck R. TGF-beta signaling in cancer--a double-edged sword. Trends Cell Biol. 2001;11:S44–S51. PubMed
Nawshad A, Hay ED. TGFbeta3 signaling activates transcription of the LEF1 gene to induce epithelial mesenchymal transformation during mouse palate development. J Cell Biol. 2003;163:1291–1301. PubMed PMC
Border WA, Okuda S, Languino LR, Sporn MB, Ruoslahti E. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor beta 1. Nature. 1990;346:371–374. PubMed
Jiménez SA, Castro SV, Piera-Velázquez S. Role of growth factors in the pathogenesis of tissue fibrosis in systemic sclerosis. Curr Rheumatol Rev. 2010;6:283–294. PubMed
Meng X-M, Nikolic-Paterson DJ, Lan HY. TGF-β: the master regulator of fibrosis. Nat Rev Nephrol. 2016;12:325–338. PubMed
Pohlers D, Brenmoehl J, Löffler I, Müller CK, Leipner C, Schultze-Mosgau S, Stallmach A, Kinne RW, Wolf G. TGF-β and fibrosis in different organs—molecular pathway imprints. Biochim Biophys Acta (BBA) - Mol Basis Dis. 1792;2009:746–756. PubMed
Sime PJ, Xing Z, Graham FL, Csaky KG, Gauldie J. Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. J Clin Invest. 1997;100:768–776. PubMed PMC
Goumenos DS, Tsamandas AC, Oldroyd S, Sotsiou F, Tsakas S, Petropoulou C, Bonikos D, El Nahas AM, Vlachojannis JG. Transforming growth factor-beta(1) and myofibroblasts: a potential pathway towards renal scarring in human glomerular disease. Nephron. 2001;87:240–248. PubMed
Molina-Molina M, Serrano-Mollar A, Bulbena O, Fernandez-Zabalegui L, Closa D, Marin-Arguedas A, Torrego A, Mullol J, Picado C, Xaubet A. Losartan attenuates bleomycin induced lung fibrosis by increasing prostaglandin E2 synthesis. Thorax. 2006;61:604–610. PubMed PMC
Fan JM, Ng YY, Hill PA, Nikolic-Paterson DJ, Mu W, Atkins RC, Lan HY. Transforming growth factor-beta regulates tubular epithelial-myofibroblast transdifferentiation in vitro. Kidney Int. 1999;56:1455–1467. PubMed
Lijnen PJ, Petrov VV, Fagard RH. Induction of cardiac fibrosis by transforming growth factor-beta(1) Mol Genet Metab. 2000;71:418–435. PubMed
Presser LD, McRae S, Waris G. Activation of TGF-β1 promoter by hepatitis C virus-induced AP-1 and Sp1: role of TGF-β1 in hepatic stellate cell activation and invasion. PLoS ONE [Internet]. 2013 [cited 2020 May 25]; 8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578869/ PubMed PMC
Milani S, Herbst H, Schuppan D, Stein H, Surrenti C. Transforming growth factors beta 1 and beta 2 are differentially expressed in fibrotic liver disease. Am J Pathol. 1991;139:1221–1229. PubMed PMC
Bernasconi P, Di Blasi C, Mora M, Morandi L, Galbiati S, Confalonieri P, Cornelio F, Mantegazza R. Transforming growth factor-beta1 and fibrosis in congenital muscular dystrophies. Neuromuscul Disord NMD. 1999;9:28–33. PubMed
Ferreira RR, da Silva Abreu R, Vilar-Pereira G, Degrave W, Meuser-Batista M, Ferreira NVC, da Cruz Moreira O, da Silva Gomes NL, de Souza EM, Ramos IP, Bailly S, Feige J-J, Lannes-Vieira J, et al. TGF-β inhibitor therapy decreases fibrosis and stimulates cardiac improvement in a pre-clinical study of chronic Chagas’ heart disease. PLoS Negl Trop Dis. 2019;13:e0007602. PubMed PMC
George J, Roulot D, Koteliansky VE, Bissell DM. In vivo inhibition of rat stellate cell activation by soluble transforming growth factor beta type II receptor: a potential new therapy for hepatic fibrosis. Proc Natl Acad Sci U S A. 1999;96:12719–12724. PubMed PMC
Kim D-Y, Lee S-H, Fu Y, Jing F, Kim W-Y, Hong S-B, Song J-A, Choe H, Ryu HJ, Kim M, Lim D, Kim M-S, Yun C-O, et al. Del-1, an endogenous inhibitor of TGF-β activation, attenuates fibrosis. Front Immunol [Internet]. Frontiers; 2020 [cited 2020 Apr 30]; 11. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2020.00068/full PubMed DOI PMC
Kuwahara F, Kai H, Tokuda K, Kai M, Takeshita A, Egashira K, Imaizumi T. Transforming growth factor-beta function blocking prevents myocardial fibrosis and diastolic dysfunction in pressure-overloaded rats. Circulation. 2002;106:130–135. doi: 10.1161/01.cir.0000020689.12472.e0. PubMed DOI
Wei Y, Kim TJ, Peng DH, Duan D, Gibbons DL, Yamauchi M, Jackson JR, Saux CJL, Calhoun C, Peters J, Derynck R, Backes BJ, Chapman HA. Fibroblast-specific inhibition of TGF-β1 signaling attenuates lung and tumor fibrosis. J Clin Invest Am Soc Clin Invest. 2017;127:3675–3688. PubMed PMC
Stone RC, Pastar I, Ojeh N, Chen V, Liu S, Garzon KI, Tomic-Canic M. Epithelial-mesenchymal transition in tissue repair and fibrosis. Cell Tissue Res. 2016;365:495–506. PubMed PMC
Bujor AM, Asano Y, Haines P, Lafyatis R, Trojanowska M. The c-Abl tyrosine kinase controls protein kinase Cδ-induced Fli-1 phosphorylation in human dermal fibroblasts. Arthritis Rheum. 2011;63:1729–1737. PubMed PMC
Caraci F, Gili E, Calafiore M, Failla M, La Rosa C, Crimi N, Sortino MA, Nicoletti F, Copani A, Vancheri C. TGF-beta1 targets the GSK-3beta/beta-catenin pathway via ERK activation in the transition of human lung fibroblasts into myofibroblasts. Pharmacol Res. 2008;57:274–282. PubMed
Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003;425:577–584. PubMed
Urist MR. Bone: formation by autoinduction. Science. 1965;150:893–899. PubMed
Wozney JM. The bone morphogenetic protein family and osteogenesis. Mol Reprod Dev. 1992;32:160–167. PubMed
Hogan BL. Bone morphogenetic proteins in development. Curr Opin Genet Dev. 1996;6:432–438. PubMed
Wagner DO, Sieber C, Bhushan R, Börgermann JH, Graf D, Knaus P. BMPs: from bone to body morphogenetic proteins. Sci Signal. 2010;3:mr1. PubMed
Herrera B, Addante A, Sánchez A. BMP Signalling at the crossroad of liver fibrosis and regeneration. Int J Mol Sci [Internet]. 2017 [cited 2020 May 7]; 19. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795989/ PubMed PMC
Weiskirchen R, Meurer SK. BMP-7 counteracting TGF-beta1 activities in organ fibrosis. Front Biosci. 2013;18:1407–1434. PubMed
Bragdon B, Moseychuk O, Saldanha S, King D, Julian J, Nohe A. Bone morphogenetic proteins: a critical review. Cell Signal. 2011;23:609–620. PubMed
Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors Chur Switz. 2004;22:233–241. PubMed
Jeffery TK, Upton PD, Trembath RC, Morrell NW. BMP4 inhibits proliferation and promotes myocyte differentiation of lung fibroblasts via Smad1 and JNK pathways. Am J Physiol-Lung Cell Mol Physiol Am Physiol Soc. 2005;288:L370–L378. PubMed
Rivera-Feliciano J, Tabin CJ. Bmp2 instructs cardiac progenitors to form the heart-valve-inducing field. Dev Biol. 2006;295:580–588. PubMed PMC
Zhang H, Bradley A. Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development. 1996;122:2977–2986. PubMed
Blázquez-Medela AM, Jumabay M, Boström KI. Beyond the Bone: bone morphogenetic protein (BMP) signaling in adipose tissue. Obes Rev Off J Int Assoc Study Obes. 2019;20:648–658. PubMed PMC
Jin W, Takagi T, Kanesashi S, Kurahashi T, Nomura T, Harada J, Ishii S. Schnurri-2 controls BMP-dependent adipogenesis via interaction with Smad proteins. Dev Cell. 2006;10:461–471. PubMed
Gerjevic LN, Liu N, Lu S, Harrison-Findik DD. Alcohol activates TGF-beta but inhibits BMP receptor-mediated Smad signaling and Smad4 binding to hepcidin promoter in the liver. Int J Hepatol [Internet]. 2012 [cited 2020 May 7]; 2012. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202137/ PubMed PMC
Nakatsuka R, Taniguchi M, Hirata M, Shiota G, Sato K. Transient expression of bone morphogenic protein-2 in acute liver injury by carbon tetrachloride. J Biochem (Tokyo) 2006;141(1):113–119. doi: 10.1093/jb/mvm012.. PubMed DOI
Shen H, Huang G, Hadi M, Choy P, Zhang M, Minuk GY, Chen Y, Gong Y. Transforming growth factor-β1 downregulation of Smad1 gene expression in rat hepatic stellate cells. Am J Physiol-Gastrointest Liver Physiol Am Physiol Soc. 2003;285:G539–G546. PubMed
Wang S, Sun A, Li L, Zhao G, Jia J, Wang K, Ge J, Zou Y. Up-regulation of BMP-2 antagonizes TGF-β1/ROCK-enhanced cardiac fibrotic signalling through activation of Smurf1/Smad6 complex. J Cell Mol Med. 2012;16:2301–2310. PubMed PMC
Yang Y-L, Ju H-Z, Liu S-F, Lee T-C, Shih Y-W, Chuang L-Y, Guh J-Y, Yang Y-Y, Liao T-N, Hung T-J, Hung M-Y. BMP-2 suppresses renal interstitial fibrosis by regulating epithelial–mesenchymal transition. J Cell Biochem. 2011;112:2558–2565. PubMed
Yang Y-L, Liu Y-S, Chuang L-Y, Guh J-Y, Lee T-C, Liao T-N, Hung M-Y, Chiang T-A. Bone morphogenetic protein-2 antagonizes renal interstitial fibrosis by promoting catabolism of type i transforming growth factor-β receptors. Endocrinology. 2009;150:727–740. PubMed
De Langhe E, Cailotto F, De Vooght V, Aznar-Lopez C, Vanoirbeek JA, Luyten FP, Lories RJU. Enhanced endogenous bone morphogenetic protein signaling protects against bleomycin induced pulmonary fibrosis. Respir Res [Internet]. 2015 [cited 2020 May 25]; 16. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364322/ PubMed PMC
Shlyonsky V, Soussia IB, Naeije R, Mies F. Opposing effects of bone morphogenetic protein-2 and endothelin-1 on lung fibroblast chloride currents. Am J Respir Cell Mol Biol. 2011;45(6):1154–1160. doi: 10.1165/rcmb.2010-0443OC. PubMed DOI
Selman M, Pardo A, Kaminski N. Idiopathic pulmonary fibrosis: aberrant recapitulation of developmental programs? PLoS Med. 2008;5:e62. PubMed PMC
Gao X, Cao Y, Yang W, Duan C, Aronson JF, Rastellini C, Chao C, Hellmich MR, Ko TC. BMP2 inhibits TGF-β-induced pancreatic stellate cell activation and extracellular matrix formation. Am J Physiol Gastrointest Liver Physiol. 2013;304:G804–G813. PubMed PMC
Gao X, Cao Y, Staloch DA, Gonzales MA, Aronson JF, Chao C, Hellmich MR, Ko TC. Bone morphogenetic protein signaling protects against cerulein-induced pancreatic fibrosis. PLoS One. 2014;9:e89114. PubMed PMC
Liang P, Huang X, Jian B, Long J, Yang X, Liu Z, Lei S. Bone morphogenetic protein 2 is involved in the proliferation and collagen synthesis of human hyperplastic scar fibroblasts. 2016.
Liu W, Selever J, Wang D, Lu M-F, Moses KA, Schwartz RJ, Martin JF. Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling. Proc Natl Acad Sci. 2004;101:4489–4494. PubMed PMC
Selever J, Liu W, Lu M-F, Behringer RR, Martin JF. Bmp4 in limb bud mesoderm regulates digit pattern by controlling AER development. Dev Biol. 2004;276:268–279. PubMed
Zhang Y, Zhang Z, Zhao X, Yu X, Hu Y, Geronimo B, Fromm SH, Chen YP. A new function of BMP4: dual role for BMP4 in regulation of Sonic hedgehog expression in the mouse tooth germ. Development. 2000;127:1431–1443. PubMed
Winnier G, Blessing M, Labosky PA, Hogan BL. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev. 1995;9:2105–2116. PubMed
Lawson KA, Dunn NR, Roelen BAJ, Zeinstra LM, Davis AM, Wright CVE, Korving JPWFM, Hogan BLM. Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev. 1999;13:424–436. PubMed PMC
Molloy EL, Adams A, Moore JB, Masterson JC, Madrigal-Estebas L, Mahon BP, O’Dea S. BMP4 induces an epithelial–mesenchymal transition-like response in adult airway epithelial cells. Growth Factors. 2008;26:12–22. PubMed
Pegorier S, Campbell GA, Kay AB, Lloyd CM. Bone morphogenetic protein (BMP)-4 and BMP-7 regulate differentially transforming growth factor (TGF)-β1 in normal human lung fibroblasts (NHLF) Respir Res. 2010;11:85. PubMed PMC
Yao M, Li J, Yuan S, Zhu X, Hu Z, Li Q, Cao R, Wang W, Fang C. Role of the arecoline/YAP1/BMP4 pathway in promoting endothelial-mesenchymal transition in oral submucous fibrosis. J Oral Pathol Med. 2020;49:305–310. PubMed
Mano Y, Yoshio S, Shoji H, Tomonari S, Aoki Y, Aoyanagi N, Okamoto T, Matsuura Y, Osawa Y, Kimura K, Yugawa K, Wang H, Oda Y, et al. Bone morphogenetic protein 4 provides cancer-supportive phenotypes to liver fibroblasts in patients with hepatocellular carcinoma. J Gastroenterol. 2019;54:1007–1018. PubMed
Omar R, Yang J, Alrushaid S, Burczynski FJ, Minuk GY, Gong Y. Inhibition of BMP4 and alpha smooth muscle actin expression in LX-2 hepatic stellate cells by BMP4-siRNA lipid based nanoparticle. J Pharm Pharm Sci. 2018;21:119–134. PubMed
Fan J, Shen H, Sun Y, Li P, Burczynski F, Namaka M, Gong Y. Bone morphogenetic protein 4 mediates bile duct ligation induced liver fibrosis through activation of Smad1 and ERK1/2 in rat hepatic stellate cells. J Cell Physiol. 2006;207:499–505. PubMed
Lu J-W, Hsia Y, Yang W-Y, Lin Y-I, Li C-C, Tsai T-F, Chang K-W, Shieh GS, Tsai S-F, Wang H-D, Yuh C-H. Identification of the common regulators for hepatocellular carcinoma induced by hepatitis B virus X antigen in a mouse model. Carcinogenesis. 2012;33:209–219. PubMed
Zhong W, Shen W-F, Ning B-F, Hu P-F, Lin Y, Yue H-Y, Yin C, Hou J-L, Chen Y-X, Zhang J-P, Zhang X, Xie W-F. Inhibition of extracellular signal-regulated kinase 1 by adenovirus mediated small interfering RNA attenuates hepatic fibrosis in rats. Hepatol Baltim Md. 2009;50:1524–1536. PubMed
Azibani F, Fazal L, Chatziantoniou C, Samuel J-L, Delcayre C. La fibrose dans l’hypertension artérielle : une histoire d’équilibre. Ann Cardiol Angeiol. 2012;61:150–155. PubMed
Sun B, Huo R, Sheng Y, Li Y, Xie X, Chen C, Liu H-B, Li N, Li C-B, Guo W-T, Zhu J-X, Yang B-F, Dong D-L. Bone morphogenetic protein-4 mediates cardiac hypertrophy, apoptosis, and fibrosis in experimentally pathological cardiac hypertrophy. Hypertension. 2013;61:352–360. PubMed
Tominaga T, Abe H, Ueda O, Goto C, Nakahara K, Murakami T, Matsubara T, Mima A, Nagai K, Araoka T, Kishi S, Fukushima N, Jishage K, et al. Activation of bone morphogenetic protein 4 signaling leads to glomerulosclerosis that mimics diabetic nephropathy. J Biol Chem. 2011;286:20109–20116. PubMed PMC
Kluk MW, Ji Y, Shin EH, Amrani O, Onodera J, Jackson WM, Nesti LJ. Fibroregulation of mesenchymal progenitor cells by BMP-4 after traumatic muscle injury. J Orthop Trauma. 2012;26:693–698. PubMed
de Mara CS, Duarte ASS, Sartori-Cintra AR, Luzo ACM, Saad STO, Coimbra IB. Chondrogenesis from umbilical cord blood cells stimulated with BMP-2 and BMP-6. Rheumatol Int. 2013;33:121–128. PubMed
Hughes FJ, Collyer J, Stanfield M, Goodman SA. The effects of bone morphogenetic protein-2, -4, and -6 on differentiation of rat osteoblast cells in vitro. Endocrinology. 1995;136:2671–2677. PubMed
Ye F, Xu H, Yin H, Zhao X, Li D, Zhu Q, Wang Y. The role of BMP6 in the proliferation and differentiation of chicken cartilage cells. PLoS One. 2019;14:e0204384. PubMed PMC
Sugiura K, Su Y-Q, Eppig JJ. Does bone morphogenetic protein 6 (BMP6) affect female fertility in the mouse? Biol Reprod. 2010;83:997–1004. PubMed PMC
Dendooven A, van Oostrom O, van der Giezen DM, Willem Leeuwis J, Snijckers C, Joles JA, Robertson EJ, Verhaar MC, Nguyen TQ, Goldschmeding R. Loss of endogenous bone morphogenetic protein-6 aggravates renal fibrosis. Am J Pathol. 2011;178:1069–1079. PubMed PMC
Yan J, Yang S, Zhang J, Zhu T. BMP6 reverses TGF-β1-induced changes in HK-2 cells: implications for the treatment of renal fibrosis. Acta Pharmacol Sin. 2009;30:994–1000. PubMed PMC
Yano R, Golbar HM, Izawa T, Sawamoto O, Kuwamura M, Yamate J. Participation of bone morphogenetic protein (BMP)-6 and osteopontin in cisplatin (CDDP)-induced rat renal fibrosis. Exp Toxicol Pathol. 2015;67:99–107. PubMed
Arndt S, Wacker E, Dorn C, Koch A, Saugspier M, Thasler WE, Hartmann A, Bosserhoff AK, Hellerbrand C. Enhanced expression of BMP6 inhibits hepatic fibrosis in non-alcoholic fatty liver disease. Gut. 2015;64:973–981. PubMed
Verhamme FM, De Smet EG, Van Hooste W, Delanghe J, Verleden SE, Joos GF, Brusselle GG, Bracke KR. Bone morphogenetic protein 6 (BMP-6) modulates lung function, pulmonary iron levels and cigarette smoke-induced inflammation. Mucosal Immunol. 2019;12:340–351. PubMed
Arndt S, Karrer S, Hellerbrand C, Bosserhoff AK. Bone morphogenetic protein-6 inhibits fibrogenesis in scleroderma offering treatment options for fibrotic skin disease. J Invest Dermatol. 2019;139:1914–1924. PubMed
Kaiser S, Schirmacher P, Philipp A, Protschka M, Moll I, Nicol K, Blessing M. Induction of bone morphogenetic protein-6 in skin wounds. Delayed reepitheliazation and scar formation in BMP-6 overexpressing transgenic mice. J Invest Dermatol. 1998;111:1145–1152. PubMed
Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, Kalluri R. BMP-7 counteracts TGF-β1–induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med. 2003;9:964–968. PubMed
Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119:1420–1428. PubMed PMC
Li RX, Yiu WH, Tang SCW. Role of bone morphogenetic protein-7 in renal fibrosis. Front Physiol [Internet]. Frontiers; 2015 [cited 2020 Apr 30]; 6. Available from: https://www.frontiersin.org/articles/10.3389/fphys.2015.00114/full PubMed PMC
Li X, An G, Wang Y, Liang D, Zhu Z, Lian X, Niu P, Guo C, Tian L. Anti-fibrotic effects of bone morphogenetic protein-7-modified bone marrow mesenchymal stem cells on silica-induced pulmonary fibrosis. Exp Mol Pathol. 2017;102(1):70–77. doi: 10.1016/j.yexmp.2016.12.010. PubMed DOI
Weiskirchen R, Meurer SK, Gressner OA, Herrmann J, Borkham-Kamphorst E, Gressner AM. BMP-7 as antagonist of organ fibrosis. Front Biosci. 2009;14:4992–5012. PubMed
Meng X-M, Chung ACK, Lan HY. Role of the TGF-β/BMP-7/Smad pathways in renal diseases. Clin Sci. 2013;124:243–254. PubMed
Miyazawa K, Shinozaki M, Hara T, Furuya T, Miyazono K. Two major Smad pathways in TGF-beta superfamily signalling. Genes Cells Devoted Mol Cell Mech. 2002;7:1191–1204. PubMed
Miyazono K, Kamiya Y, Morikawa M. Bone morphogenetic protein receptors and signal transduction. J Biochem (Tokyo) 2010;147:35–51. PubMed
Mueller TD, Nickel J. Promiscuity and specificity in BMP receptor activation. FEBS Lett. 2012;586:1846–1859. PubMed
Wang S, Hirschberg R. Bone morphogenetic protein-7 signals opposing transforming growth factor beta in mesangial cells. J Biol Chem. 2004;279:23200–23206. PubMed
Yan X, Liu Z, Chen Y. Regulation of TGF-beta signaling by Smad7. Acta Biochim Biophys Sin. 2009;41:263–272. PubMed PMC
Kinoshita K, Iimuro Y, Otogawa K, Saika S, Inagaki Y, Nakajima Y, Kawada N, Fujimoto J, Friedman SL, Ikeda K. Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats. Gut. 2007;56:706–714. PubMed PMC
Zou G-L, Zuo S, Lu S, Hu R-H, Lu Y-Y, Yang J, Deng K-S, Wu Y-T, Mu M, Zhu J-J, Zeng J-Z, Zhang B-F, Wu X, et al. Bone morphogenetic protein-7 represses hepatic stellate cell activation and liver fibrosis via regulation of TGF-β/Smad signaling pathway. World J Gastroenterol. 2019;25:4222–4234. PubMed PMC
Chen B-L, Peng J, Li Q-F, Yang M, Wang Y, Chen W. Exogenous bone morphogenetic protein-7 reduces hepatic fibrosis in Schistosoma japonicum-infected mice via transforming growth factor-β/Smad signaling. World J Gastroenterol: WJG. 2013;19:1405–1415. PubMed PMC
Guo J, Lin Q, Shao Y, Rong L, Zhang D. BMP-7 suppresses excessive scar formation by activating the BMP-7/Smad1/5/8 signaling pathway. Mol Med Rep. 2017;16:1957–1963. PubMed PMC
Hao Z-M, Cai M, Lv Y-F, Huang Y-H, Li H-H. Oral Administration of recombinant adeno-associated virus-mediated bone morphogenetic protein-7 suppresses CCl4-induced hepatic fibrosis in mice. Mol Ther. 2012;20:2043–2051. PubMed PMC
Wang L-P, Dong J-Z, Xiong L-J, Shi K-Q, Zou Z-L, Zhang S-N, Cao S-T, Lin Z, Chen Y-P. BMP-7 attenuates liver fibrosis via regulation of epidermal growth factor receptor. Int J Clin Exp Pathol. 2014;7:3537–3547. PubMed PMC
Ivanac-Janković R, Ćorić M, Furić-Čunko V, Lovičić V, Bašić-Jukić N, Kes P. BMP-7 protein expression is downregulated in human diabetic nephropathy. Acta Clin Croat. 2015;54:164–168. PubMed
Lee S-Y, Kim SI, Choi ME. Therapeutic targets for treating fibrotic kidney diseases. Transl Res J Lab Clin Med. 2015;165:512–530. PubMed PMC
Chen X, Xu J, Jiang B, Liu D. Bone Morphogenetic protein-7 antagonizes myocardial fibrosis induced by atrial fibrillation by restraining transforming growth factor-β (TGF-β)/Smads signaling. Med Sci Monit Int Med J Exp Clin Res. 2016;22:3457–3468. PubMed PMC
Murray LA, Hackett TL, Warner SM, Shaheen F, Argentieri RL, Dudas P, Farrell FX, Knight DA. BMP-7 does not protect against bleomycin-induced lung or skin fibrosis. PLoS ONE [Internet]. 2008 [cited 2020 Aug 20]; 3. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2603595/ PubMed PMC
Kang Q, Sun MH, Cheng H, Peng Y, Montag AG, Deyrup AT, Jiang W, Luu HH, Luo J, Szatkowski JP, Vanichakarn P, Park JY, Li Y, et al. Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery. Gene Ther. 2004;11(17):1312–1320. doi: 10.1038/sj.gt.3302298. PubMed DOI
Lopez-Coviella I, Follettie MT, Mellott TJ, Kovacheva VP, Slack BE, Diesl V, Berse B, Thies RS, Blusztajn JK. Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons. Proc Natl Acad Sci U S A. 2005;102:6984–6989. PubMed PMC
Truksa J, Peng H, Lee P, Beutler E. Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Proc Natl Acad Sci U S A. 2006;103:10289–10293. PubMed PMC
Breitkopf-Heinlein K, Meyer C, König C, Gaitantzi H, Addante A, Thomas M, Wiercinska E, Cai C, Li Q, Wan F, Hellerbrand C, Valous NA, Hahnel M, et al. BMP-9 interferes with liver regeneration and promotes liver fibrosis. Gut. 2017;66:939–954. PubMed
Munoz Felix JM, Salgado CM. A better understanding of the role of TGF-β family members in tissue fibrosis. J Cell Signal [Internet]. 2016 [cited 2020 May 11]; 01. Available from: https://www.omicsonline.org/open-access/a-better-understanding-of-the-role-of-tgf-family-members-in-tissuefibrosis.php?aid=84072
Addante A, Roncero C, Almalé L, Lazcanoiturburu N, García-Álvaro M, Fernández M, Sanz J, Hammad S, Nwosu ZC, Lee S-J, Fabregat I, Dooley S, Ten Dijke P, et al. Bone morphogenetic protein 9 as a key regulator of liver progenitor cells in DDC-induced cholestatic liver injury. Liver Int Off J Int Assoc Study Liver. 2018;38(9):1664–1675. doi: 10.1111/liv.13879. PubMed DOI PMC
Li P, Li Y, Zhu L, Yang Z, He J, Wang L, Shang Q, Pan H, Wang H, Ma X, Li B, Fan X, Ge S, et al. Targeting secreted cytokine BMP9 gates the attenuation of hepatic fibrosis. Biochim Biophys Acta (BBA) - Mol Basis Dis. 1864;2018:709–720. PubMed
Li Q, Liu B, Breitkopf-Heinlein K, Weng H, Jiang Q, Dong P, Dooley S, Xu K, Ding H. Adenovirus-mediated overexpression of bone morphogenetic protein-9 promotes methionine choline deficiency-induced non-alcoholic steatohepatitis in non-obese mice. Mol Med Rep. 2019;20:2743–2753. PubMed PMC
Muñoz-Félix JM, Cuesta C, Perretta-Tejedor N, Subileau M, López-Hernández FJ, López-Novoa JM, Martínez-Salgado C. Identification of bone morphogenetic protein 9 (BMP9) as a novel profibrotic factor in vitro. Cell Signal. 2016;28:1252–1261. PubMed
Ly T, Agnès D-C, Christine M, Laurent G, Amélie C, Carole P, Florian R, Raphaël T, Jennifer B, Ayumi S, Alice H, Olli R, Laurent S, et al. Selective BMP-9 inhibition partially protects against experimental pulmonary hypertension. Circ Res Am Heart Assoc. 2019;124:846–855. PubMed
Chen X, Orriols M, Walther FJ, Laghmani EH, Hoogeboom AM, Hogen-Esch ACB, Hiemstra PS, Folkerts G, Goumans M-JTH, ten Dijke P, Morrell NW, Wagenaar GTM. Bone morphogenetic protein 9 protects against neonatal hyperoxia-induced impairment of alveolarization and pulmonary inflammation. Front Physiol [Internet]. Frontiers; 2017 [cited 2020 May 25]; 8. Available from: https://www.frontiersin.org/articles/10.3389/fphys.2017.00486/full PubMed PMC
Liu R, Hu W, Li X, Pu D, Yang G, Liu H, Tan M, Zhu D. Association of circulating BMP9 with coronary heart disease and hypertension in Chinese populations. BMC Cardiovasc Disord. 2019;19(1):131. doi: 10.1186/s12872-019-1095-2. PubMed DOI PMC
Morine KJ, Qiao X, York S, Natov PS, Paruchuri V, Zhang Y, Aronovitz MJ, Karas RH, Kapur NK. Bone morphogenetic protein 9 reduces cardiac fibrosis and improves cardiac function in heart failure. Circulation. 2018;138:513–526. PubMed PMC
Coleman CM, Loredo GA, Lo CW, Tuan RS. Correlation of GDF5 and connexin 43 mRNA expression during embryonic development. Anat Rec A Discov Mol Cell Evol Biol. 2003;275:1117–1121. PubMed
Nishitoh H, Ichijo H, Kimura M, Matsumoto T, Makishima F, Yamaguchi A, Yamashita H, Enomoto S, Miyazono K. Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5. J Biol Chem. 1996;271:21345–21352. PubMed
Storm EE, Huynh TV, Copeland NG, Jenkins NA, Kingsley DM, Lee SJ. Limb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily. Nature. 1994;368:639–643. PubMed
Chen H, Yong W, Ren S, Shen W, He Y, Cox KA, Zhu W, Li W, Soonpaa M, Payne RM, Franco D, Field LJ, Rosen V, et al. Overexpression of bone morphogenetic protein 10 in myocardium disrupts cardiac postnatal hypertrophic growth. J Biol Chem. 2006;281:27481–27491. PubMed PMC
Nakahara T, Tominaga K, Koseki T, Yamamoto M, Yamato K, Fukuda J, Nishihara T. Growth/differentiation factor-5 induces growth arrest and apoptosis in mouse B lineage cells with modulation by Smad. Cell Signal. 2003;15:181–187. PubMed
Yamashita H, Shimizu A, Kato M, Nishitoh H, Ichijo H, Hanyu A, Morita I, Kimura M, Makishima F, Miyazono K. Growth/differentiation factor-5 induces angiogenesisin vivo. Exp Cell Res. 1997;235:218–226. PubMed
Zeng Q, Li X, Beck G, Balian G, Shen FH. Growth and differentiation factor-5 (GDF-5) stimulates osteogenic differentiation and increases vascular endothelial growth factor (VEGF) levels in fat-derived stromal cells in vitro. Bone. 2007;40:374–381. PubMed
Zaidi SHE, Huang Q, Momen A, Riazi A, Husain M. Growth differentiation factor 5 regulates cardiac repair after myocardial infarction. J Am Coll Cardiol. 2010;55:135–143. PubMed
Yao Y, Zhang J, Ye D, Tan D, Peng J, Xie M, Fang L. Left-right determination factor is down-regulated in fibrotic renal tissue of human hydronephrosis. BJU Int. 2011;107:1002–1008. PubMed
McPherron AC. Metabolic functions of myostatin and GDF11. Immunol Endocr Metab Agents Med Chem. 2010;10:217–231. PubMed PMC
Sharma M, McFarlane C, Kambadur R, Kukreti H, Bonala S, Srinivasan S. Myostatin: expanding horizons. IUBMB Life. 2015;67:589–600. PubMed
Dong J, Dong Y, Chen Z, Mitch WE, Zhang L. The pathway to muscle fibrosis depends on myostatin stimulating the differentiation of fibro/adipogenic progenitor cells in chronic kidney disease. Kidney Int. 2017;91:119–128. PubMed PMC
Bogdanovich S, Krag TOB, Barton ER, Morris LD, Whittemore L-A, Ahima RS, Khurana TS. Functional improvement of dystrophic muscle by myostatin blockade. Nature. 2002;420:418–421. PubMed
Li ZB, Zhang J, Wagner KR. Inhibition of myostatin reverses muscle fibrosis through apoptosis. J Cell Sci. 2012;125:3957–3965. PubMed
Li ZB, Kollias HD, Wagner KR. Myostatin directly regulates skeletal muscle fibrosis. J Biol Chem. 2008;283:19371–19378. PubMed PMC
McCroskery S, Thomas M, Platt L, Hennebry A, Nishimura T, McLeay L, Sharma M, Kambadur R. Improved muscle healing through enhanced regeneration and reduced fibrosis in myostatin-null mice. J Cell Sci. 2005;118:3531–3541. PubMed
Nakatani M, Takehara Y, Sugino H, Matsumoto M, Hashimoto O, Hasegawa Y, Murakami T, Uezumi A, Takeda S, Noji S, Sunada Y, Tsuchida K. Transgenic expression of a myostatin inhibitor derived from follistatin increases skeletal muscle mass and ameliorates dystrophic pathology in mdx mice. FASEB J Off Publ Fed Am Soc Exp Biol. 2008;22:477–487. PubMed
Ohno Y, Matsuba Y, Hashimoto N, Sugiura T, Ohira Y, Yoshioka T, Goto K. Suppression of myostatin stimulates regenerative potential of injured antigravitational soleus muscle in mice under unloading condition. Int J Med Sci. 2016;13:680–685. PubMed PMC
Biesemann N, Mendler L, Kostin S, Wietelmann A, Borchardt T, Braun T. Myostatin induces interstitial fibrosis in the heart via TAK1 and p38. Cell Tissue Res. 2015;361:779–787. PubMed
Breitbart A, Auger-Messier M, Molkentin JD, Heineke J. Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting. Am J Physiol Heart Circ Physiol. 2011;300:H1973–H1982. PubMed PMC
Morissette MR, Stricker JC, Rosenberg MA, Buranasombati C, Levitan EB, Mittleman MA, Rosenzweig A. Effects of myostatin deletion in aging mice. Aging Cell. 2009;8:573–583. PubMed PMC
Caligiuri A, Delogu W, Provenzano A, Galastri S, Pinzani M, Marra F. T-26 The myostatin system is expressed in the liver and its activation mediates profibrogenic actions via c-Jun N-terminal kinase. Dig Liver Dis. 2013;45:S21–S22.
Delogu W, Caligiuri A, Provenzano A, Rosso C, Bugianesi E, Coratti A, Macias-Barragan J, Galastri S, Maira GD, Marra F. Myostatin regulates the fibrogenic phenotype of hepatic stellate cells via c-jun N-terminal kinase activation. Dig Liver. 2019;51:1400–1408. PubMed
Nishikawa H, Enomoto H, Ishii A, Iwata Y, Miyamoto Y, Ishii N, Yuri Y, Hasegawa K, Nakano C, Nishimura T, Yoh K, Aizawa N, Sakai Y, et al. Elevated serum myostatin level is associated with worse survival in patients with liver cirrhosis. J Cachexia Sarcopenia Muscle. 2017;8:915–925. PubMed PMC
Katoh Y, Katoh M. Comparative integromics on BMP/GDF family. Int J Mol Med. 2006;17:951–955. PubMed
Nakashima M, Toyono T, Akamine A, Joyner A. Expression of growth/differentiation factor 11, a new member of the BMP/TGFbeta superfamily during mouse embryogenesis. Mech Dev. 1999;80:185–189. PubMed
Zhang Y, Wei Y, Liu D, Liu F, Li X, Pan L, Pang Y, Chen D. Role of growth differentiation factor 11 in development, physiology and disease. Oncotarget. 2017;8:81604–81616. PubMed PMC
Khalil AM, Dotimas H, Kahn J, Lamerdin JE, Hayes DB, Gupta P, Franti M. Differential binding activity of TGF-β family proteins to select TGF-β receptors. J Pharmacol Exp Ther Am Soc Pharmacol Exp Ther. 2016;358:423–430. PubMed
Camici GG, Savarese G, Akhmedov A, Lüscher TF. Molecular mechanism of endothelial and vascular aging: implications for cardiovascular disease. Eur Heart J. 2015;36:3392–3403. PubMed
Rochette L, Zeller M, Cottin Y, Vergely C. Growth and differentiation factor 11 (GDF11): Functions in the regulation of erythropoiesis and cardiac regeneration. Pharmacol Ther. 2015;156:26–33. PubMed
Demontis F, Patel VK, Swindell WR, Perrimon N. Inter-tissue Control of the nucleolus via a myokine-dependent longevity pathway. Cell Rep. 2014;7:1481–1494. PubMed PMC
Wang Z, Dou M, Liu F, Jiang P, Ye S, Ma L, Cao H, Du X, Sun P, Su N, Lin F, Zhang R, Li C. GDF11 induces differentiation and apoptosis and inhibits migration of C17.2 neural stem cells via modulating MAPK signaling pathway. PeerJ [Internet]. 2018 [cited 2020 May 12]; 6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128255/ PubMed PMC
Esquela AF, Lee S-J. Regulation of metanephric kidney development by growth/differentiation factor 11. Dev Biol. 2003;257(2):356–370. doi: 10.1016/s0012-1606(03)00100-3. PubMed DOI
Harmon EB, Apelqvist AA, Smart NG, Gu X, Osborne DH, Kim SK. GDF11 modulates NGN3+ islet progenitor cell number and promotes beta-cell differentiation in pancreas development. Dev Camb Engl. 2004;131:6163–6174. PubMed
McPherron AC, Huynh TV, Lee S-J. Redundancy of myostatin and growth/differentiation factor 11 function. BMC Dev Biol. 2009;9:24. PubMed PMC
Wu H-H, Ivkovic S, Murray RC, Jaramillo S, Lyons KM, Johnson JE, Calof AL. Autoregulation of neurogenesis by GDF11. Neuron. 2003;37:197–207. PubMed
Bajikar SS, Wang C-C, Borten MA, Pereira EJ, Atkins KA, Janes KA. Tumor suppressor inactivation of GDF11 occurs by precursor sequestration in triple-negative breast cancer. Dev Cell. 2017;43:418–435. PubMed PMC
Gerardo-Ramírez M, Lazzarini-Lechuga R, Hernández-Rizo S, Jiménez-Salazar JE, Simoni-Nieves A, García-Ruiz C, Fernández-Checa JC, Marquardt JU, Coulouarn C, Gutiérrez-Ruiz MC, Pérez-Aguilar B, Gomez-Quiroz LE. GDF11 exhibits tumor suppressive properties in hepatocellular carcinoma cells by restricting clonal expansion and invasion. Biochim Biophys Acta (BBA) - Mol Basis Dis. 1865;2019:1540–1554. PubMed
Qin X, Kuang H, Chen L, Wei S, Yu D, Liang F. Coexpression of growth differentiation factor 11 and reactive oxygen species in metastatic oral cancer and its role in inducing the epithelial to mesenchymal transition. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;123:697–706. PubMed
Simoni-Nieves A, Gerardo-Ramírez M, Pedraza-Vázquez G, Chávez-Rodríguez L, Bucio L, Souza V, Miranda-Labra RU, Gomez-Quiroz LE, Gutiérrez-Ruiz MC. GDF11 implications in cancer biology and metabolism. Facts and controversies. Front Oncol [Internet]. 2019 [cited 2020 Apr 15]; 9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803553/ PubMed PMC
Yokoe T, Ohmachi T, Inoue H, Mimori K, Tanaka F, Kusunoki M, Mori M. Clinical significance of growth differentiation factor 11 in colorectal cancer. Int J Oncol. 2007;31(5):1097–1101. PubMed
Loffredo FS, Steinhauser ML, Jay SM, Gannon J, Pancoast JR, Yalamanchi P, Sinha M, Dall’Osso C, Khong D, Shadrach JL, Miller CM, Singer BS, Stewart A, et al. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell. 2013;153:828–839. PubMed PMC
Sinha M, Jang YC, Oh J, Khong D, Wu EY, Manohar R, Miller C, Regalado SG, Loffredo FS, Pancoast JR, Hirshman MF, Lebowitz J, Shadrach JL, et al. Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science. 2014;344:649–652. PubMed PMC
Li H, Li Y, Xiang L, Zhang J, Zhu B, Xiang L, Dong J, Liu M, Xiang G. GDF11 attenuates development of type 2 diabetes via improvement of islet β-cell function and survival. Diabetes. 2017;66:1914–1927. PubMed
Finkenzeller G, Stark GB, Strassburg S. Growth differentiation factor 11 supports migration and sprouting of endothelial progenitor cells. J Surg Res. 2015;198:50–56. PubMed
Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS, Wojtkiewicz GR, Chen JW, Lee RT, Wagers AJ, Rubin LL. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science. 2014;344:630–634. PubMed PMC
Zhang W, Guo Y, Li B, Zhang Q, Liu J, Gu G, Wang J, Bao R, Chen Y, Xu J. GDF11 rejuvenates cerebrovascular structure and function in an animal model of Alzheimer’s disease. J Alzheimers Dis. 2018;62:807–819. PubMed
Ozek C, Krolewski RC, Buchanan SM, Rubin LL. Growth differentiation factor 11 treatment leads to neuronal and vascular improvements in the hippocampus of aged mice. Sci Rep. 2018;8:17293. PubMed PMC
Egerman MA, Cadena SM, Gilbert JA, Meyer A, Nelson HN, Swalley SE, Mallozzi C, Jacobi C, Jennings LL, Clay I, Laurent G, Ma S, Brachat S, et al. GDF11 increases with age and inhibits skeletal muscle regeneration. Cell Metab. 2015;22:164–174. PubMed PMC
Egerman MA, Glass DJ. The role of GDF11 in aging and skeletal muscle, cardiac and bone homeostasis. Crit Rev Biochem Mol Biol. 2019;54:174–183. PubMed
Hinken AC, Powers JM, Luo G, Holt JA, Billin AN, Russell AJ. Lack of evidence for GDF11 as a rejuvenator of aged skeletal muscle satellite cells. Aging Cell. 2016;15:582–584. PubMed PMC
Rodgers BD, Eldridge JA. Reduced circulating GDF11 is unlikely responsible for age-dependent changes in mouse heart, muscle, and brain. Endocrinology. 2015;156:3885–3888. PubMed
Smith SC, Zhang X, Zhang X, Gross P, Starosta T, Mohsin S, Franti M, Gupta P, Hayes D, Myzithras M, Kahn J, Tanner J, Weldon SM, et al. GDF11 Does not rescue aging-related pathological hypertrophy. Circ Res. 2015;117:926–932. PubMed PMC
Hammers DW, Merscham-Banda M, Hsiao JY, Engst S, Hartman JJ, Sweeney HL. Supraphysiological levels of GDF11 induce striated muscle atrophy. EMBO Mol Med. 2017;9:531–544. PubMed PMC
Harper SC, Jaslyn J, Giulia B, Huaqing Z, Tao W, Markus W, Hajime K, Feldsott Eric A, Yijun Y, Yunichel J, Xinji G, Karim SA, Priyanka G, et al. GDF11 decreases pressure overload–induced hypertrophy, but can cause severe cachexia and premature death. Circ Res. 2018;123:1220–1231. PubMed PMC
Jones JE, Cadena SM, Gong C, Wang X, Chen Z, Wang SX, Vickers C, Chen H, Lach-Trifilieff E, Hadcock JR, Glass DJ. Supraphysiologic administration of GDF11 induces cachexia in part by upregulating GDF15. Cell Rep Elsevier. 2018;22:1522–1530. PubMed
Onodera K, Sugiura H, Yamada M, Koarai A, Fujino N, Yanagisawa S, Tanaka R, Numakura T, Togo S, Sato K, Kyogoku Y, Hashimoto Y, Okazaki T, et al. Decrease in an anti-ageing factor, growth differentiation factor 11, in chronic obstructive pulmonary disease. Thorax. 2017;72:893–904. PubMed
Kwapiszewska G, Gungl A, Wilhelm J, Marsh LM, Thekkekara Puthenparampil H, Sinn K, Didiasova M, Klepetko W, Kosanovic D, Schermuly RT, Wujak L, Weiss B, Schaefer L, et al. Transcriptome profiling reveals the complexity of pirfenidone effects in idiopathic pulmonary fibrosis. Eur Respir J. 2018;52:1800564. PubMed
Zhang Y, Li Q, Liu D, Huang Q, Cai G, Cui S, Sun X, Chen X. GDF11 improves tubular regeneration after acute kidney injury in elderly mice. Sci Rep. 2016;6:1–15. PubMed PMC
Pons M, Koniaris LG, Moe SM, Gutierrez JC, Esquela-Kerscher A, Zimmers TA. GDF11 induces kidney fibrosis, renal cell epithelial-to-mesenchymal transition and kidney dysfunction and failure. Surgery. 2018;164:262–273. PubMed PMC
Du G-Q, Shao Z-B, Wu J, Yin W-J, Li S-H, Wu J, Weisel RD, Tian J-W, Li R-K. Targeted myocardial delivery of GDF11 gene rejuvenates the aged mouse heart and enhances myocardial regeneration after ischemia–reperfusion injury. Basic Res Cardiol. 2016;112:7. PubMed
Poggioli T, Vujic A, Yang P, Macias-Trevino C, Uygur A, Loffredo FS, Pancoast JR, Cho M, Goldstein J, Tandias RM, Gonzalez E, Walker RG, Thompson TB, et al. Circulating growth differentiation factor 11/8 levels decline with age. Circ Res. 2016;118:29–37. PubMed PMC
Zimmers TA, Jiang Y, Wang M, Liang TW, Rupert JE, Au ED, Marino FE, Couch ME, Koniaris LG. Exogenous GDF11 induces cardiac and skeletal muscle dysfunction and wasting. Basic Res Cardiol. 2017;112:48. PubMed PMC
Cingolani OH, Yang X-P, Liu Y-H, Villanueva M, Rhaleb N-E, Carretero OA. Reduction of cardiac fibrosis decreases systolic performance without affecting diastolic function in hypertensive rats. Hypertens Dallas Tex 1979. 2004;43:1067–1073. PubMed PMC
Heymans S, Schroen B, Vermeersch P, Milting H, Gao F, Kassner A, Gillijns H, Herijgers P, Flameng W, Carmeliet P, Van de Werf F, Pinto YM, Janssens S. Increased cardiac expression of tissue inhibitor of metalloproteinase-1 and tissue inhibitor of metalloproteinase-2 is related to cardiac fibrosis and dysfunction in the chronic pressure-overloaded human heart. Circulation. 2005;112:1136–1144. PubMed
Xia Y, Lee K, Li N, Corbett D, Mendoza L, Frangogiannis NG. Characterization of the inflammatory and fibrotic response in a mouse model of cardiac pressure overload. Histochem Cell Biol. 2009;131:471–481. PubMed PMC
Garbern J, Kristl AC, Bassaneze V, Vujic A, Schoemaker H, Sereda R, Peng L, Ricci-Blair EM, Goldstein JM, Walker RG, Bhasin S, Wagers AJ, Lee RT. Analysis of Cre-mediated genetic deletion of Gdf11 in cardiomyocytes of young mice. Am J Physiol-Heart Circ Physiol. 2019;317:H201–H212. PubMed PMC
Pugach EK, Richmond PA, Azofeifa JG, Dowell RD, Leinwand LA. Prolonged Cre expression driven by the α-myosin heavy chain promoter can be cardiotoxic. J Mol Cell Cardiol. 2015;86:54–61. PubMed PMC
Jin Q, Qiao C, Li J, Xiao B, Li J, Xiao X. A GDF11/myostatin inhibitor, GDF11 propeptide-Fc, increases skeletal muscle mass and improves muscle strength in dystrophic mdx mice. Skelet Muscle [Internet]. 2019 [cited 2020 Apr 27]; 9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537384/ PubMed PMC
Gutpell KM, Hrinivich WT, Hoffman LM. Skeletal muscle fibrosis in the mdx/utrn+/- mouse validates its suitability as a murine model of duchenne muscular dystrophy. PLoS ONE. 2015;10(1):e0117306. doi: 10.1371/journal.pone.0117306. PubMed DOI PMC
Pessina P, Cabrera D, Morales MG, Riquelme CA, Gutiérrez J, Serrano AL, Brandan E, Muñoz-Cánoves P. Novel and optimized strategies for inducing fibrosis in vivo: focus on Duchenne Muscular Dystrophy. Skelet Muscle. 2014;4:7. doi: 10.1186/2044-5040-4-7. PubMed DOI PMC
Rinaldi F, Zhang Y, Mondragon-Gonzalez R, Harvey J, Perlingeiro R. Treatment with rGDF11 does not improve the dystrophic muscle pathology of mdx mice. Skelet Muscle. 2016; 6. PubMed PMC
Zhou Y, Sharma N, Dukes D, Myzithras MB, Gupta P, Khalil A, Kahn J, Ahlberg JS, Hayes DB, Franti M, Criswell T. GDF11 Treatment attenuates the recovery of skeletal muscle function after injury in older rats. AAPS J. 2017;19:431–437. PubMed
Li Q, Jiao L, Shao Y, Li M, Gong M, Zhang Y, Tan Z, Wang Y, Yang X, Wang Z, Zhang Y. Topical GDF11 accelerates skin wound healing in both type 1 and 2 diabetic mouse models. Biochem Biophys Res Commun. 2020;529:7–14. PubMed
Rochette L, Mazini L, Meloux A, Zeller M, Cottin Y, Vergely C, Malka G. Anti-aging effects of GDF11 on skin. Int J Mol Sci [Internet]. 2020 [cited 2020 Jul 21]; 21. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177281/ PubMed PMC
Tito A, Barbulova A, Zappelli C, Leone M, Ruvo M, Mercurio FA, Chambery A, Russo R, Colucci MG, Apone F. The growth differentiation factor 11 is involved in skin fibroblast ageing and is induced by a preparation of peptides and sugars derived from plant cell cultures. Mol Biotechnol. 2019;61(3):209–220. doi: 10.1007/s12033-019-00154-w. PubMed DOI
Dai Z, Song G, Balakrishnan A, Yang T, Yuan Q, Möbus S, Weiss A-C, Bentler M, Zhu J, Jiang X, Shen X, Bantel H, Jaeckel E, et al. Growth differentiation factor 11 attenuates liver fibrosis via expansion of liver progenitor cells. Gut [Internet]. BMJ Publishing Group; 2019 [cited 2020 Apr 23]; Available from: https://gut.bmj.com/content/early/2019/11/29/gutjnl-2019-318812 PubMed PMC
Frohlich J. GDF11 induces mild hepatic fibrosis independent of metabolic health. Ageing. 2020 (in review). PubMed PMC
Nagahashi M, Matsuda Y, Moro K, Tsuchida J, Soma D, Hirose Y, Kobayashi T, Kosugi S-I, Takabe K, Komatsu M, Wakai T. DNA damage response and sphingolipid signaling in liver diseases. Surg Today. 2016;46:995–1005. PubMed PMC
Yan J, Tung H-C, Li S, Niu Y, Garbacz WG, Lu P, Bi Y, Li Y, He J, Xu M, Ren S, Monga SP, Schwabe RF, et al. Aryl hydrocarbon receptor signaling prevents activation of hepatic stellate cells and liver fibrogenesis in mice. Gastroenterology. 2019;157:793–806. PubMed PMC
Cardio- and Neurometabolic Adipobiology: Consequences and Implications for Therapy