-
Something wrong with this record ?
Heterogeneous response to TGF-β1/3 isoforms in fibroblasts of different origins: implications for wound healing and tumorigenesis
L. Urban, M. Čoma, L. Lacina, P. Szabo, J. Sabová, T. Urban, H. Šuca, Š. Lukačín, R. Zajíček, K. Smetana, P. Gál
Language English Country Germany
Document type Journal Article
Grant support
VEGA-1/0561/18, 1/0319/20 and 1/0455/22
Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
APVV-20-0017 and APVV-22-0006
Agentúra na Podporu Výskumu a Vývoja
Cooperatio ONCO
Univerzita Karlova v Praze
CZ.02.1.01/0.0/0.0/16_019/0000785 and LX22NPO5102
European Regional Development Fund
NLK
ProQuest Central
from 1997-01-01 to 1 year ago
Medline Complete (EBSCOhost)
from 2000-01-01 to 1 year ago
Nursing & Allied Health Database (ProQuest)
from 1997-01-01 to 1 year ago
Health & Medicine (ProQuest)
from 1997-01-01 to 1 year ago
Public Health Database (ProQuest)
from 1997-01-01 to 1 year ago
- MeSH
- Fibroblasts metabolism MeSH
- Wound Healing MeSH
- Cicatrix, Hypertrophic * metabolism pathology MeSH
- Carcinogenesis metabolism pathology MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Cell Transformation, Neoplastic metabolism MeSH
- Protein Isoforms metabolism MeSH
- Transforming Growth Factor beta metabolism MeSH
- Transforming Growth Factor beta1 * pharmacology metabolism MeSH
- Transforming Growth Factor beta3 metabolism pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Identification of therapeutic targets for treating fibrotic diseases and cancer remains challenging. Our study aimed to investigate the effects of TGF-β1 and TGF-β3 on myofibroblast differentiation and extracellular matrix deposition in different types of fibroblasts, including normal/dermal, cancer-associated, and scar-derived fibroblasts. When comparing the phenotype and signaling pathways activation we observed extreme heterogeneity of studied markers across different fibroblast populations, even within those isolated from the same tissue. Specifically, the presence of myofibroblast and deposition of extracellular matrix were dependent on the origin of the fibroblasts and the type of treatment they received (TGF-β1 vs. TGF-β3). In parallel, we detected activation of canonical signaling (pSMAD2/3) across all studied fibroblasts, albeit to various extents. Treatment with TGF-β1 and TGF-β3 resulted in the activation of canonical and several non-canonical pathways, including AKT, ERK, and ROCK. Among studied cells, cancer-associated fibroblasts displayed the most heterogenic response to TGF-β1/3 treatments. In general, TGF-β1 demonstrated a more potent activation of signaling pathways compared to TGF-β3, whereas TGF-β3 exhibited rather an inhibitory effect in keloid- and hypertrophic scar-derived fibroblasts suggesting its clinical potential for scar treatment. In summary, our study has implications for comprehending the role of TGF-β signaling in fibroblast biology, fibrotic diseases, and cancer. Future research should focus on unraveling the mechanisms beyond differential fibroblast responses to TGF-β isomers considering inherent fibroblast heterogeneity.
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc24000481
- 003
- CZ-PrNML
- 005
- 20250603084534.0
- 007
- ta
- 008
- 240109s2023 gw f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1007/s00418-023-02221-5 $2 doi
- 035 __
- $a (PubMed)37707642
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a gw
- 100 1_
- $a Urban, Lukáš $u Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, 040 11, Košice, Slovak Republic $u Department of Biomedical Research, East-Slovak Institute of Cardiovascular Diseases Inc, Ondavská, 040 11, Košice, Slovak Republic $1 https://orcid.org/0000000327694295
- 245 10
- $a Heterogeneous response to TGF-β1/3 isoforms in fibroblasts of different origins: implications for wound healing and tumorigenesis / $c L. Urban, M. Čoma, L. Lacina, P. Szabo, J. Sabová, T. Urban, H. Šuca, Š. Lukačín, R. Zajíček, K. Smetana, P. Gál
- 520 9_
- $a Identification of therapeutic targets for treating fibrotic diseases and cancer remains challenging. Our study aimed to investigate the effects of TGF-β1 and TGF-β3 on myofibroblast differentiation and extracellular matrix deposition in different types of fibroblasts, including normal/dermal, cancer-associated, and scar-derived fibroblasts. When comparing the phenotype and signaling pathways activation we observed extreme heterogeneity of studied markers across different fibroblast populations, even within those isolated from the same tissue. Specifically, the presence of myofibroblast and deposition of extracellular matrix were dependent on the origin of the fibroblasts and the type of treatment they received (TGF-β1 vs. TGF-β3). In parallel, we detected activation of canonical signaling (pSMAD2/3) across all studied fibroblasts, albeit to various extents. Treatment with TGF-β1 and TGF-β3 resulted in the activation of canonical and several non-canonical pathways, including AKT, ERK, and ROCK. Among studied cells, cancer-associated fibroblasts displayed the most heterogenic response to TGF-β1/3 treatments. In general, TGF-β1 demonstrated a more potent activation of signaling pathways compared to TGF-β3, whereas TGF-β3 exhibited rather an inhibitory effect in keloid- and hypertrophic scar-derived fibroblasts suggesting its clinical potential for scar treatment. In summary, our study has implications for comprehending the role of TGF-β signaling in fibroblast biology, fibrotic diseases, and cancer. Future research should focus on unraveling the mechanisms beyond differential fibroblast responses to TGF-β isomers considering inherent fibroblast heterogeneity.
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a transformující růstový faktor beta1 $x farmakologie $x metabolismus $7 D053773
- 650 _2
- $a transformující růstový faktor beta3 $x metabolismus $x farmakologie $7 D053782
- 650 _2
- $a fibroblasty $x metabolismus $7 D005347
- 650 _2
- $a hojení ran $7 D014945
- 650 12
- $a jizva hypertrofická $x metabolismus $x patologie $7 D017439
- 650 _2
- $a transformující růstový faktor beta $x metabolismus $7 D016212
- 650 _2
- $a karcinogeneze $x metabolismus $x patologie $7 D063646
- 650 _2
- $a nádorová transformace buněk $x metabolismus $7 D002471
- 650 _2
- $a protein - isoformy $x metabolismus $7 D020033
- 650 _2
- $a kultivované buňky $7 D002478
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Čoma, Matúš $u Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, 040 11, Košice, Slovak Republic $u Department of Biomedical Research, East-Slovak Institute of Cardiovascular Diseases Inc, Ondavská, 040 11, Košice, Slovak Republic $1 https://orcid.org/0000000244502083 $7 xx0264880
- 700 1_
- $a Lacina, Lukáš $u Institute of Anatomy, First Faculty of Medicine, Charles University, U Nemocnice 2, 128 00, Prague, Czech Republic $u BIOCEV, First Faculty of Medicine, Charles University, 252 50, Vestec, Czech Republic $u Department Dermatovenereology, First Faculty of Medicine, Charles University and General University Hospital, 128 08, Prague, Czech Republic $1 https://orcid.org/0000000217509933 $7 xx0106429
- 700 1_
- $a Szabo, Pavol $u Institute of Anatomy, First Faculty of Medicine, Charles University, U Nemocnice 2, 128 00, Prague, Czech Republic $u BIOCEV, First Faculty of Medicine, Charles University, 252 50, Vestec, Czech Republic $1 https://orcid.org/0000000219441493 $7 xx0145899
- 700 1_
- $a Sabová, Jana $u Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, 040 11, Košice, Slovak Republic $1 https://orcid.org/0009000628218150
- 700 1_
- $a Urban, Tomáš $u Prague Burn Center, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, 100 00, Prague, Czech Republic $1 https://orcid.org/0000000150610585
- 700 1_
- $a Šuca, Hubert $u Prague Burn Center, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, 100 00, Prague, Czech Republic $1 https://orcid.org/0000000156555572
- 700 1_
- $a Lukačín, Štefan, $d 1969- $u Department of Heart Surgery, East-Slovak Institute of Cardiovascular Diseases Inc, 040 11, Košice, Slovak Republic $1 https://orcid.org/0000000159225958 $7 xx0322399
- 700 1_
- $a Zajíček, Robert $u Prague Burn Center, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, 100 00, Prague, Czech Republic $1 https://orcid.org/0000000273725315 $7 xx0098569
- 700 1_
- $a Smetana, Karel $u Institute of Anatomy, First Faculty of Medicine, Charles University, U Nemocnice 2, 128 00, Prague, Czech Republic. karel.smetana@lf1.cuni.cz $u BIOCEV, First Faculty of Medicine, Charles University, 252 50, Vestec, Czech Republic. karel.smetana@lf1.cuni.cz $1 https://orcid.org/0000000278788403 $7 jn20000710554
- 700 1_
- $a Gál, Peter $u Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, 040 11, Košice, Slovak Republic. galovci@yahoo.com $u Department of Biomedical Research, East-Slovak Institute of Cardiovascular Diseases Inc, Ondavská, 040 11, Košice, Slovak Republic. galovci@yahoo.com $u Prague Burn Center, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, 100 00, Prague, Czech Republic. galovci@yahoo.com $u Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, 832 32, Bratislava, Slovak Republic. galovci@yahoo.com $u Institute of Neurobiology, Biomedical Research Center of the Slovak Academy of Sciences, 040 01, Košice, Slovak Republic. galovci@yahoo.com $1 https://orcid.org/0000000233983408 $7 xx0126576
- 773 0_
- $w MED00002042 $t Histochemistry and cell biology $x 1432-119X $g Roč. 160, č. 6 (2023), s. 541-554
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/37707642 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20240109 $b ABA008
- 991 __
- $a 20250603084530 $b ABA008
- 999 __
- $a ok $b bmc $g 2049254 $s 1210175
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2023 $b 160 $c 6 $d 541-554 $e 20230914 $i 1432-119X $m Histochemistry and cell biology $n Histochem Cell Biol $x MED00002042
- GRA __
- $a VEGA-1/0561/18, 1/0319/20 and 1/0455/22 $p Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
- GRA __
- $a APVV-20-0017 and APVV-22-0006 $p Agentúra na Podporu Výskumu a Vývoja
- GRA __
- $a Cooperatio ONCO $p Univerzita Karlova v Praze
- GRA __
- $a CZ.02.1.01/0.0/0.0/16_019/0000785 and LX22NPO5102 $p European Regional Development Fund
- LZP __
- $a Pubmed-20240109
