Osteoprotegerin is induced by transforming growth factor-beta 1 and regulates pro-fibrotic responses in human dermal fibroblasts

IF 2.2 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical and biophysical research communications Pub Date : 2025-03-25 Epub Date: 2025-02-21 DOI:10.1016/j.bbrc.2025.151524
Aaron K. McDowell-Sanchez , Alan R. Waich Cohen , Santiago Sanchez , Konstantin Tsoyi
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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.
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骨蛋白激酶受转化生长因子-β1 的诱导,并调节人类真皮成纤维细胞的促纤维化反应
已知转化生长因子-β1 (TGF-β1)在器官纤维化的进展中起关键作用。在这里,我们证明了TGF-β1在蛋白和mRNA水平上诱导人真皮成纤维细胞(HDFs)中骨保护素(OPG)的表达。OPG中和导致HDFs中TGF-β1介导的纤维化作用减弱。此外,我们发现重组OPG诱导纤维连接蛋白(FN)的产生和α-平滑肌肌动蛋白(α-SMA)的表达。有趣的是,αvβ3-整合素抑制剂(cyclo(RGDfK)和西伦吉肽)显著减弱了OPG介导的作用,这表明OPG通过调节αvβ3-整合素的激活在人真皮成纤维细胞中发挥促纤维化作用。综上所述,我们的数据表明,TGF-β1可以刺激OPG的表达,并有助于真皮成纤维细胞的激活。
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来源期刊
Biochemical and biophysical research communications
Biochemical and biophysical research communications 生物-生化与分子生物学
CiteScore
6.10
自引率
0.00%
发文量
1400
审稿时长
14 days
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
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