Exploring the Role of GDF-15 in Inflammatory Bowel Disease: A Case-Controlled Study Comparing Crohn's Disease and Ulcerative Colitis with Non-Inflammatory Controls

. 2024 Mar 25 ; 14 (4) : . [epub] 20240325

Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid38668313

Grantová podpora
Specific research SV/FVZ202201 Ministry of Education, Youth and Sports of the Czech Republic
projects MO 1012 (Military University Hospital Prague, Czech Republic) and MO 1011 - Clinical Fields II (Military Faculty of Medicine, University of Defence, Hradec Kralove, Czech Republic) Ministry of Defence of the Czech Republic

Inflammatory bowel disease, encompassing Crohn's disease and ulcerative colitis, is a persistent immune-mediated inflammatory gastrointestinal disease. This study investigates the role of growth differentiation factor 15 in severe IBD cases, aiming to identify a reliable parameter to assess disease severity and monitor activity. We analyzed plasma samples from 100 patients undergoing biologic therapy for severe IBD and 50 control subjects. Our analysis included evaluations of GDF-15 levels, inflammatory markers, and clinical features. We employed statistical methods such as the Mann-Whitney U test, ANOVA, and Spearman's correlation for an in-depth analysis. Our results demonstrated consistently higher GDF-15 levels in patients with both Crohn's disease and ulcerative colitis compared to the control group, irrespective of the biologic treatment received. The correlation analysis indicated significant relationships between GDF-15 levels, patient age, fibrinogen, and IL-6 levels. This study positions GDF-15 as a promising biomarker for severe IBD, with notable correlations with age and inflammatory markers. These findings underscore GDF-15's potential in enhancing disease monitoring and management strategies in an IBD context and encourage further research to clarify GDF-15's role in the IBD pathophysiology.

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Bootcov M.R., Bauskin A.R., Valenzuela S.M., Moore A.G., Bansal M., He X.Y., Zhang H.P., Donnellan M., Mahler S., Pryor K., et al. MIC-1, a Novel Macrophage Inhibitory Cytokine, Is a Divergent Member of the TGF-β Superfamily. Proc. Natl. Acad. Sci. USA. 1997;94:11514–11519. doi: 10.1073/pnas.94.21.11514. PubMed DOI PMC

Lawton L.N., Bonaldo M.D.F., Jelenc P.C., Qiu L., Baumes S.A., Marcelino R.A., De Jesus G.M., Wellington S., Knowles J.A., Warburton D., et al. Identification of a Novel Member of the TGF-Beta Superfamily Highly Expressed in Human Placenta. Gene. 1997;203:17–26. doi: 10.1016/S0378-1119(97)00485-X. PubMed DOI

Hromas R., Hufford M., Sutton J., Xu D., Li Y., Lu L. PLAB, a Novel Placental Bone Morphogenetic Protein. Biochim. Biophys. Acta (BBA) Gene Struct. Expr. 1997;1354:40–44. doi: 10.1016/S0167-4781(97)00122-X. PubMed DOI

Baek S.J., Horowitz J.M., Eling T.E. Molecular Cloning and Characterization of Human Nonsteroidal Anti-Inflammatory Drug-Activated Gene Promoter. J. Biol. Chem. 2001;276:33384–33392. doi: 10.1074/jbc.M101814200. PubMed DOI

Gordon K.J., Blobe G.C. Role of Transforming Growth Factor-β Superfamily Signaling Pathways in Human Disease. Biochim. Biophys. Acta (BBA) Mol. Basis Dis. 2008;1782:197–228. doi: 10.1016/j.bbadis.2008.01.006. PubMed DOI

Santibañez J.F., Quintanilla M., Bernabeu C. TGF-β/TGF-β Receptor System and Its Role in Physiological and Pathological Conditions. Clin. Sci. 2011;121:233–251. doi: 10.1042/CS20110086. PubMed DOI

De Caestecker M. The Transforming Growth Factor-β Superfamily of Receptors. Cytokine Growth Factor Rev. 2004;15:1–11. doi: 10.1016/j.cytogfr.2003.10.004. PubMed DOI

Siegel P.M., Massagué J. Cytostatic and Apoptotic Actions of TGF-β in Homeostasis and Cancer. Nat. Rev. Cancer. 2003;3:807–820. doi: 10.1038/nrc1208. PubMed DOI

Battegay E.J., Raines E.W., Seifert R.A., Bowen-Pope D.F., Ross R. TGF-β Induces Bimodal Proliferation of Connective Tissue Cells via Complex Control of an Autocrine PDGF Loop. Cell. 1990;63:515–524. doi: 10.1016/0092-8674(90)90448-N. PubMed DOI

Xu X., Zheng L., Yuan Q., Zhen G., Crane J.L., Zhou X., Cao X. Transforming Growth Factor-β in Stem Cells and Tissue Homeostasis. Bone Res. 2018;6:2. doi: 10.1038/s41413-017-0005-4. PubMed DOI PMC

Assadi A., Zahabi A., Hart R.A. GDF15, an Update of the Physiological and Pathological Roles It Plays: A Review. Pflug. Arch. Eur. J. Physiol. 2020;472:1535–1546. doi: 10.1007/s00424-020-02459-1. PubMed DOI

Wang D., Day E.A., Townsend L.K., Djordjevic D., Jørgensen S.B., Steinberg G.R. GDF15: Emerging Biology and Therapeutic Applications for Obesity and Cardiometabolic Disease. Nat. Rev. Endocrinol. 2021;17:592–607. doi: 10.1038/s41574-021-00529-7. PubMed DOI

Böttner M., Laaff M., Schechinger B., Rappold G., Unsicker K., Suter-Crazzolara C. Characterization of the Rat, Mouse, and Human Genes of Growth/Differentiation Factor-15/Macrophage Inhibiting Cytokine-1 (GDF-15/MIC-1) Gene. 1999;237:105–111. doi: 10.1016/S0378-1119(99)00309-1. PubMed DOI

Mimeault M., Batra S.K. Divergent Molecular Mechanisms Underlying the Pleiotropic Functions of Macrophage Inhibitory Cytokine-1 in Cancer. J. Cell. Physiol. 2010;224:626–635. doi: 10.1002/jcp.22196. PubMed DOI PMC

Koopmann J., Buckhaults P., Brown D.A., Zahurak M.L., Sato N., Fukushima N., Sokoll L.J., Chan D.W., Yeo C.J., Hruban R.H., et al. Serum Macrophage Inhibitory Cytokine 1 as a Marker of Pancreatic and Other Periampullary Cancers. Clin. Cancer Res. 2004;10:2386–2392. doi: 10.1158/1078-0432.CCR-03-0165. PubMed DOI

Strelau J., Strzelczyk A., Rusu P., Bendner G., Wiese S., Diella F., Altick A.L., Von Bartheld C.S., Klein R., Sendtner M., et al. Progressive Postnatal Motoneuron Loss in Mice Lacking GDF-15. J. Neurosci. 2009;29:13640–13648. doi: 10.1523/JNEUROSCI.1133-09.2009. PubMed DOI PMC

Lambert J.R., Kelly J.A., Shim M., Huffer W.E., Nordeen S.K., Baek S.J., Eling T.E., Lucia M.S. Prostate Derived Factor in Human Prostate Cancer Cells: Gene Induction by Vitamin D via a P53-dependent Mechanism and Inhibition of Prostate Cancer Cell Growth. J. Cell. Physiol. 2006;208:566–574. doi: 10.1002/jcp.20692. PubMed DOI

Yokoyama-Kobayashi M., Saeki M., Sekine S., Kato S. Human cDNA Encoding a Novel TGF- Superfamily Protein Highly Expressed in Placenta. J. Biochem. 1997;122:622–626. doi: 10.1093/oxfordjournals.jbchem.a021798. PubMed DOI

Kim K.H., Kim S.H., Han D.H., Jo Y.S., Lee Y., Lee M.-S. Growth Differentiation Factor 15 Ameliorates Nonalcoholic Steatohepatitis and Related Metabolic Disorders in Mice. Sci. Rep. 2018;8:6789. doi: 10.1038/s41598-018-25098-0. PubMed DOI PMC

Kleinert M., Clemmensen C., Sjøberg K.A., Carl C.S., Jeppesen J.F., Wojtaszewski J.F.P., Kiens B., Richter E.A. Exercise Increases Circulating GDF15 in Humans. Mol. Metab. 2018;9:187–191. doi: 10.1016/j.molmet.2017.12.016. PubMed DOI PMC

Tsai V.W.-W., Macia L., Feinle-Bisset C., Manandhar R., Astrup A., Raben A., Lorenzen J.K., Schmidt P.T., Wiklund F., Pedersen N.L., et al. Serum Levels of Human MIC-1/GDF15 Vary in a Diurnal Pattern, Do Not Display a Profile Suggestive of a Satiety Factor and Are Related to BMI. PLoS ONE. 2015;10:e0133362. doi: 10.1371/journal.pone.0133362. PubMed DOI PMC

Ananthakrishnan A.N., Adler J., Chachu K.A., Nguyen N.H., Siddique S.M., Weiss J.M., Sultan S., Velayos F.S., Cohen B.L., Singh S. AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn’s Disease. Gastroenterology. 2023;165:1367–1399. doi: 10.1053/j.gastro.2023.09.029. PubMed DOI

Peyrin-Biroulet L., Sandborn W., Sands B.E., Reinisch W., Bemelman W., Bryant R.V., D’Haens G., Dotan I., Dubinsky M., Feagan B., et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. Am. J. Gastroenterol. 2015;110:1324–1338. doi: 10.1038/ajg.2015.233. PubMed DOI

Gerstein H.C., Pare G., Hess S., Ford R.J., Sjaarda J., Raman K., McQueen M., Lee S., Haenel H., Steinberg G.R. Growth Differentiation Factor 15 as a Novel Biomarker for Metformin. Diabetes Care. 2017;40:280–283. doi: 10.2337/dc16-1682. PubMed DOI

Al-kuraishy H.M., Al-Gareeb A.I., Alexiou A., Papadakis M., Nadwa E.H., Albogami S.M., Alorabi M., Saad H.M., Batiha G.E. Metformin and Growth Differentiation Factor 15 (GDF15) in Type 2 Diabetes Mellitus: A Hidden Treasure. J. Diabetes. 2022;14:806–814. doi: 10.1111/1753-0407.13334. PubMed DOI PMC

Welsh J.B., Sapinoso L.M., Kern S.G., Brown D.A., Liu T., Bauskin A.R., Ward R.L., Hawkins N.J., Quinn D.I., Russell P.J., et al. Large-Scale Delineation of Secreted Protein Biomarkers Overexpressed in Cancer Tissue and Serum. Proc. Natl. Acad. Sci. USA. 2003;100:3410–3415. doi: 10.1073/pnas.0530278100. PubMed DOI PMC

Johnen H., Lin S., Kuffner T., Brown D.A., Tsai V.W.-W., Bauskin A.R., Wu L., Pankhurst G., Jiang L., Junankar S., et al. Tumor-Induced Anorexia and Weight Loss Are Mediated by the TGF-β Superfamily Cytokine MIC-1. Nat. Med. 2007;13:1333–1340. doi: 10.1038/nm1677. PubMed DOI

He Y.-W., He C.-S. Association of Growth and Differentiation Factor 15 in Rheumatoid Arthritis. J. Inflamm. Res. 2022;15:1173–1181. doi: 10.2147/JIR.S350281. PubMed DOI PMC

Akbari H., Talaee R., Zaker S.F., Nikoueinejad H. Investigating the Correlation between Growth Differentiation Factor 15 Serum Level and Its Gene Expression with Psoriasis and Its Severity. Iran. J. Allergy Asthma Immunol. 2021;20:593–599. doi: 10.18502/ijaai.v20i5.7409. PubMed DOI

Elbarky E.M., Hussien M.I., Elgazzar N.M., Mabrouk M.M., Elsaadany H.M. Serum Growth Differentiation Factor-15 (GDF-15) Level in Behcet’s Disease Patients: Relation to Clinical Characteristics, Musculoskeletal Ultrasound Findings and Disease Activity. Egypt. Rheumatol. 2021;43:261–266. doi: 10.1016/j.ejr.2021.05.002. DOI

Fuchs T., Trollor J.N., Crawford J., Brown D.A., Baune B.T., Samaras K., Campbell L., Breit S.N., Brodaty H., Sachdev P., et al. Macrophage Inhibitory Cytokine-1 Is Associated with Cognitive Impairment and Predicts Cognitive Decline—The Sydney Memory and Aging Study. Aging Cell. 2013;12:882–889. doi: 10.1111/acel.12116. PubMed DOI

Chai Y.L., Hilal S., Chong J.P.C., Ng Y.X., Liew O.W., Xu X., Ikram M.K., Venketasubramanian N., Richards A.M., Lai M.K.P., et al. Growth Differentiation Factor-15 and White Matter Hyperintensities in Cognitive Impairment and Dementia. Medicine. 2016;95:e4566. doi: 10.1097/MD.0000000000004566. PubMed DOI PMC

Bouabdallaoui N., Claggett B., Zile M.R., McMurray J.J.V., O’Meara E., Packer M., Prescott M.F., Swedberg K., Solomon S.D., Rouleau J.L., et al. Growth Differentiation Factor-15 Is Not Modified by Sacubitril/Valsartan and Is an Independent Marker of Risk in Patients with Heart Failure and Reduced Ejection Fraction: The PARADIGM-HF Trial. Eur. J. Heart Fail. 2018;20:1701–1709. doi: 10.1002/ejhf.1301. PubMed DOI

Kempf T., Bjorklund E., Olofsson S., Lindahl B., Allhoff T., Peter T., Tongers J., Wollert K.C., Wallentin L. Growth-Differentiation Factor-15 Improves Risk Stratification in ST-Segment Elevation Myocardial Infarction. Eur. Heart J. 2007;28:2858–2865. doi: 10.1093/eurheartj/ehm465. PubMed DOI

Wollert K.C., Kempf T., Peter T., Olofsson S., James S., Johnston N., Lindahl B., Horn-Wichmann R., Brabant G., Simoons M.L., et al. Prognostic Value of Growth-Differentiation Factor-15 in Patients With Non–ST-Elevation Acute Coronary Syndrome. Circulation. 2007;115:962–971. doi: 10.1161/CIRCULATIONAHA.106.650846. PubMed DOI

Lindholm D., James S.K., Gabrysch K., Storey R.F., Himmelmann A., Cannon C.P., Mahaffey K.W., Steg P.G., Held C., Siegbahn A., et al. Association of Multiple Biomarkers With Risk of All-Cause and Cause-Specific Mortality After Acute Coronary Syndromes: A Secondary Analysis of the PLATO Biomarker Study. JAMA Cardiol. 2018;3:1160. doi: 10.1001/jamacardio.2018.3811. PubMed DOI PMC

Li M., Duan L., Cai Y.-L., Li H.-Y., Hao B.-C., Chen J.-Q., Liu H.-B. Growth Differentiation Factor-15 Is Associated with Cardiovascular Outcomes in Patients with Coronary Artery Disease. Cardiovasc. Diabetol. 2020;19:120. doi: 10.1186/s12933-020-01092-7. PubMed DOI PMC

Sharma A., Hijazi Z., Andersson U., Al-Khatib S.M., Lopes R.D., Alexander J.H., Held C., Hylek E.M., Leonardi S., Hanna M., et al. Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation: Insights From the ARISTOTLE Trial. Circulation. 2018;138:1666–1676. doi: 10.1161/CIRCULATIONAHA.118.034125. PubMed DOI

Xu J., Kimball T.R., Lorenz J.N., Brown D.A., Bauskin A.R., Klevitsky R., Hewett T.E., Breit S.N., Molkentin J.D. GDF15/MIC-1 Functions As a Protective and Antihypertrophic Factor Released From the Myocardium in Association With SMAD Protein Activation. Circ. Res. 2006;98:342–350. doi: 10.1161/01.RES.0000202804.84885.d0. PubMed DOI

Bonaterra G.A., Zügel S., Thogersen J., Walter S.A., Haberkorn U., Strelau J., Kinscherf R. Growth Differentiation Factor-15 Deficiency Inhibits Atherosclerosis Progression by Regulating Interleukin-6–Dependent Inflammatory Response to Vascular Injury. J. Am. Heart Assoc. 2012;1:e002550. doi: 10.1161/JAHA.112.002550. PubMed DOI PMC

Preusch M.R., Baeuerle M., Albrecht C., Blessing E., Bischof M., Katus H.A., Bea F. GDF-15 Protects from Macrophage Accumulation in a Mousemodel of Advanced Atherosclerosis. Eur. J. Med. Res. 2013;18:19. doi: 10.1186/2047-783X-18-19. PubMed DOI PMC

Johnen H., Kuffner T., Brown D.A., Wu B.J., Stocker R., Breit S.N. Increased Expression of the TGF-b Superfamily Cytokine MIC-1/GDF15 Protects ApoE−/− Mice from the Development of Atherosclerosis. Cardiovasc. Pathol. 2012;21:499–505. doi: 10.1016/j.carpath.2012.02.003. PubMed DOI

Nair V., Robinson-Cohen C., Smith M.R., Bellovich K.A., Bhat Z.Y., Bobadilla M., Brosius F., De Boer I.H., Essioux L., Formentini I., et al. Growth Differentiation Factor–15 and Risk of CKD Progression. J. Am. Soc. Nephrol. 2017;28:2233–2240. doi: 10.1681/ASN.2016080919. PubMed DOI PMC

Kim Y.-I., Shin H.-W., Chun Y.-S., Park J.-W. CST3 and GDF15 Ameliorate Renal Fibrosis by Inhibiting Fibroblast Growth and Activation. Biochem. Biophys. Res. Commun. 2018;500:288–295. doi: 10.1016/j.bbrc.2018.04.061. PubMed DOI

Emmerson P.J., Wang F., Du Y., Liu Q., Pickard R.T., Gonciarz M.D., Coskun T., Hamang M.J., Sindelar D.K., Ballman K.K., et al. The Metabolic Effects of GDF15 Are Mediated by the Orphan Receptor GFRAL. Nat. Med. 2017;23:1215–1219. doi: 10.1038/nm.4393. PubMed DOI

Mullican S.E., Lin-Schmidt X., Chin C.-N., Chavez J.A., Furman J.L., Armstrong A.A., Beck S.C., South V.J., Dinh T.Q., Cash-Mason T.D., et al. GFRAL Is the Receptor for GDF15 and the Ligand Promotes Weight Loss in Mice and Nonhuman Primates. Nat. Med. 2017;23:1150–1157. doi: 10.1038/nm.4392. PubMed DOI

Yang L., Chang C.-C., Sun Z., Madsen D., Zhu H., Padkjær S.B., Wu X., Huang T., Hultman K., Paulsen S.J., et al. GFRAL Is the Receptor for GDF15 and Is Required for the Anti-Obesity Effects of the Ligand. Nat. Med. 2017;23:1158–1166. doi: 10.1038/nm.4394. PubMed DOI

Bauskin A.R., Brown D.A., Kuffner T., Johnen H., Luo X.W., Hunter M., Breit S.N. Role of Macrophage Inhibitory Cytokine-1 in Tumorigenesis and Diagnosis of Cancer. Cancer Res. 2006;66:4983–4986. doi: 10.1158/0008-5472.CAN-05-4067. PubMed DOI

Siddiqui J.A., Pothuraju R., Khan P., Sharma G., Muniyan S., Seshacharyulu P., Jain M., Nasser M.W., Batra S.K. Pathophysiological Role of Growth Differentiation Factor 15 (GDF15) in Obesity, Cancer, and Cachexia. Cytokine Growth Factor Rev. 2022;64:71–83. doi: 10.1016/j.cytogfr.2021.11.002. PubMed DOI PMC

Corre J., Hébraud B., Bourin P. Concise Review: Growth Differentiation Factor 15 in Pathology: A Clinical Role? Stem Cells Transl. Med. 2013;2:946–952. doi: 10.5966/sctm.2013-0055. PubMed DOI PMC

Wallin U., Glimelius B., Jirström K., Darmanis S., Nong R.Y., Pontén F., Johansson C., Påhlman L., Birgisson H. Growth Differentiation Factor 15: A Prognostic Marker for Recurrence in Colorectal Cancer. Br. J. Cancer. 2011;104:1619–1627. doi: 10.1038/bjc.2011.112. PubMed DOI PMC

Vocka M., Langer D., Fryba V., Petrtyl J., Hanus T., Kalousova M., Zima T., Petruzelka L. Growth/Differentiation Factor 15 (GDF-15) as New Potential Serum Marker in Patients with Metastatic Colorectal Cancer. Cancer Biomark. 2018;21:869–874. doi: 10.3233/CBM-170792. PubMed DOI

Esalatmanesh K., Fayyazi H., Esalatmanesh R., Khabbazi A. The Association between Serum Levels of Growth Differentiation Factor-15 and Rheumatoid Arthritis Activity. Int. J. Clin. Pract. 2020;74:e13564. doi: 10.1111/ijcp.13564. PubMed DOI

Khalil M.E., Elhanafy M.S., Eigela S.E., Nasr H.E., ELgendy M.E. Serum GDF-15 Level in Rheumatoid Arthritis and Relation to Disease Activity and Severity. Benha J. Appl. Sci. 2020;5:131–134. doi: 10.21608/bjas.2020.136266. DOI

Taşolar M.K., Erfan G., Raimoğlu O., Albayrak H., Yanık M.E. Role of GDF-15 as an Inflammatory Marker in Patients with Psoriasis Vulgaris. Arch. Turk. Dermatol. Venerol. 2021;55:184–188. doi: 10.4274/turkderm.galenos.2021.73444. DOI

Sarıyıldız M.A., Yazmalar L., Batmaz İ., Alpaycı M., Burkan Y.K., Sula B., Kaplan İ., Yıldız M., Akar Z.A., Bozkurt M. Serum GDF -15 Level in Behçet’s Disease: Relationships between Disease Activity and Clinical Parameters. Int. J. Dermatol. 2016;55:1289–1294. doi: 10.1111/ijd.13309. PubMed DOI

Meadows C.A., Risbano M.G., Zhang L., Geraci M.W., Tuder R.M., Collier D.H., Bull T.M. Increased Expression of Growth Differentiation Factor-15 in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension. Chest. 2011;139:994–1002. doi: 10.1378/chest.10-0302. PubMed DOI PMC

Chen P., Zhou G., Lin J., Li L., Zeng Z., Chen M., Zhang S. Serum Biomarkers for Inflammatory Bowel Disease. Front. Med. 2020;7:123. doi: 10.3389/fmed.2020.00123. PubMed DOI PMC

Con D., Andrew B., Nicolaides S., Van Langenberg D.R., Vasudevan A. Biomarker Dynamics during Infliximab Salvage for Acute Severe Ulcerative Colitis: C-Reactive Protein (CRP)-Lymphocyte Ratio and CRP-Albumin Ratio Are Useful in Predicting Colectomy. Intestig. Res. 2022;20:101–113. doi: 10.5217/ir.2020.00146. PubMed DOI PMC

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