TGFβ1 induces myofibroblast transdifferentiation via increasing Smad-mediated RhoGDI-RhoGTPase signaling.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2022-11-01 DOI:10.4149/gpb_2022044

Lian Tang, Panfeng Feng, Yan Qi, Lei Huang, Xiuying Liang, Xia Chen

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引用次数: 1

Abstract

This study serves to investigate the effects of the Smad pathway on TGFβ1-mediated RhoGDI expression and its binding to RhoGTPases in myofibroblast transdifferentiation. Myofibroblast transdifferentiation was induced by TGFβ1 in vitro. Cells were pretreated with different siRNAs or inhibitors. Myofibroblast transdifferentiation was detected by immunohistochemistry. Immunofluorescence was used to observe the nuclear translocation of Smad4, and PSR (Picrositius Red) staining was used to measure collagen concentration. TGFβ1 induced the phosphorylation of Smad2/3 and the nuclear translocation of Smad4 in human aortic adventitial fibroblasts (HAAFs). Furthermore, TGFβ1 increased the expression of RhoGDI and its binding to RhoGTPases. Nevertheless, inhibition of Smad2/3 phosphorylation decreased TGFβ1-induced RhoGDI1/2 expressions and RhoGDI2-RhoGTPases interactions. These data suggested that the inhibition of Smad phosphorylation attenuates myofibroblast transdifferentiation by inhibiting TGFβ1-induced RhoGDI1/2 expressions and RhoGDI-RhoGTPases signaling.

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TGFβ1通过增加smad介导的RhoGDI-RhoGTPase信号传导诱导肌成纤维细胞转分化。

本研究旨在探讨Smad通路对tgf - β1介导的RhoGDI表达的影响及其在肌成纤维细胞转分化过程中与rhogtpase的结合。tgf - β1诱导肌成纤维细胞转分化。用不同的sirna或抑制剂预处理细胞。免疫组织化学检测肌成纤维细胞转分化。免疫荧光法观察Smad4的核易位，PSR (Picrositius Red)染色法测定胶原浓度。tgf - β1诱导人主动脉内皮成纤维细胞(HAAFs) Smad2/3磷酸化和Smad4核易位。此外，tgf - β1增加RhoGDI的表达及其与RhoGTPases的结合。然而，抑制Smad2/3磷酸化降低了tgf β1诱导的RhoGDI1/2表达和RhoGDI2-RhoGTPases的相互作用。这些数据表明，抑制Smad磷酸化可通过抑制tgf β1诱导的rhogdi /2表达和RhoGDI-RhoGTPases信号传导来减弱肌成纤维细胞的转分化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.

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