Aaron K. McDowell-Sanchez , Alan R. Waich Cohen , Santiago Sanchez , Konstantin Tsoyi
{"title":"Osteoprotegerin is induced by transforming growth factor-beta 1 and regulates pro-fibrotic responses in human dermal fibroblasts","authors":"Aaron K. McDowell-Sanchez , Alan R. Waich Cohen , Santiago Sanchez , Konstantin Tsoyi","doi":"10.1016/j.bbrc.2025.151524","DOIUrl":null,"url":null,"abstract":"<div><div>Transforming growth factor-beta1 (TGF-β1) is known to play a key role in the progression of organ fibrosis. Here, we demonstrate that TGF-β1 induces osteoprotegerin (OPG) expression in human dermal fibroblasts (HDFs) at both protein and mRNA levels. OPG neutralization has led to attenuation of TGF-β1-mediated profibrotic effects in HDFs. Further, we found that recombinant OPG induced fibronectin (FN) production and alpha-smooth muscle actin (α-SMA) expression. Interestingly, the OPG-mediated effect was significantly attenuated by αvβ3-integrin inhibitors (cyclo(RGDfK) and cilengitide) suggesting that OPG exerts profibrotic responses in human dermal fibroblasts by regulating αvβ3-integrin activation. Taken together, our data suggest that OPG expression is stimulated by TGF-β1 and contributes to dermal fibroblast activation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151524"},"PeriodicalIF":2.5000,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical and biophysical research communications","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0006291X25002384","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Transforming growth factor-beta1 (TGF-β1) is known to play a key role in the progression of organ fibrosis. Here, we demonstrate that TGF-β1 induces osteoprotegerin (OPG) expression in human dermal fibroblasts (HDFs) at both protein and mRNA levels. OPG neutralization has led to attenuation of TGF-β1-mediated profibrotic effects in HDFs. Further, we found that recombinant OPG induced fibronectin (FN) production and alpha-smooth muscle actin (α-SMA) expression. Interestingly, the OPG-mediated effect was significantly attenuated by αvβ3-integrin inhibitors (cyclo(RGDfK) and cilengitide) suggesting that OPG exerts profibrotic responses in human dermal fibroblasts by regulating αvβ3-integrin activation. Taken together, our data suggest that OPG expression is stimulated by TGF-β1 and contributes to dermal fibroblast activation.
期刊介绍:
Biochemical and Biophysical Research Communications is the premier international journal devoted to the very rapid dissemination of timely and significant experimental results in diverse fields of biological research. The development of the "Breakthroughs and Views" section brings the minireview format to the journal, and issues often contain collections of special interest manuscripts. BBRC is published weekly (52 issues/year).Research Areas now include: Biochemistry; biophysics; cell biology; developmental biology; immunology
; molecular biology; neurobiology; plant biology and proteomics