Transient Receptor Potential Channel Canonical Type 3 Deficiency Antagonizes Myofibroblast Transdifferentiation In Vivo
Transient Receptor Potential Channel Canonical Type 3 Deficiency Antagonizes Myofibroblast Transdifferentiation In Vivo
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瞬时受体电位通道典型 3 型缺陷会拮抗体内肌成纤维细胞转分化
DOI：
10.1155/2020/1202189
复制
发表时间：
2020-03
影响因子：
--
通讯作者：
Zhang Hengshu
中科院分区：
文献类型：
--
作者：
Xia Weijie;Wang Qianran;Lu Yuangang;Hu Yingru;Zhang Xingcun;Zhang Junbo;Liu Dongfang;Song Jinlin;Zhu Zhiming;Liu Daoyan;Zhang Hengshu
目的肌成纤维细胞转化与活性氧（ROS）产生酶NADPH氧化酶（Nox 4）有关。抑制瞬时受体电位通道典型3（TRPC 3）减弱高血压大鼠血管中线粒体钙处理和ROS产生。然而，TRPC 3是否调节线粒体钙和ROS的产生并参与伤口愈合过程中的肌成纤维细胞转分化仍然是难以捉摸的。方法和结果在本研究中，我们证明了转化生长因子β（TGFβ（TGFαSMA））激活TRPC 3。用TRPC 3的特异性抑制剂Pyr 3抑制TRPC 3可显著降低TGFβ（TGFαSMA）。用TRPC 3的特异性抑制剂Pyr 3抑制TRPC 3，可显著降低TGFβ（TGFβ（TGF Trpc 3 −/−小鼠表现出显著减弱的肌成纤维细胞转分化，表现为αSMA降低）。用TRPC 3的特异性抑制剂Pyr 3抑制TRPC 3可显著降低TGFβ（TGFβ（TGF Trpc 3 −/−小鼠表现出显著减弱的肌成纤维细胞转分化，如Trpc 3 +/+小鼠降低所示。此外，Trpc 3 −/−小鼠表现出显著减弱的肌成纤维细胞转分化，如降低的结论所示。我们的数据表明，TGFβ1介导的TRPC 3激活增强线粒体钙和ROS的产生，从而促进肌成纤维细胞转分化和HTS形成。抑制TRPC 3介导的Nox 4/pSmad 2/3通路可能是限制损伤后HTS形成的有用策略。
Objective Myofibroblast transformation has been shown to be associated with the reactive oxygen species- (ROS-) producing enzyme NADPH oxidase (Nox4). Inhibition of transient receptor potential channel canonical type 3 (TRPC3) attenuates mitochondrial calcium handling and ROS production in the vasculature of hypertensive rats. However, it remains elusive whether TRPC3 regulates mitochondrial calcium and ROS production and participates in myofibroblast transdifferentiation during wound healing. Methods and Results In this study, we demonstrated that activation of TRPC3 by transforming growth factor β (TGFβ (TGFαSMA). Inhibition of TRPC3 with its specific inhibitor, Pyr3, significantly decreased TGFβ (TGFαSMA). Inhibition of TRPC3 with its specific inhibitor, Pyr3, significantly decreased TGFβ (TGFβ (TGFTrpc3−/− mice exhibited significantly attenuated myofibroblast transdifferentiation, as demonstrated by decreased αSMA). Inhibition of TRPC3 with its specific inhibitor, Pyr3, significantly decreased TGFβ (TGFβ (TGFTrpc3−/− mice exhibited significantly attenuated myofibroblast transdifferentiation, as demonstrated by decreased Trpc3+/+ mice. In addition, Trpc3−/− mice exhibited significantly attenuated myofibroblast transdifferentiation, as demonstrated by decreased Conclusions Our data indicate that TGFβ1-mediated activation of TRPC3 enhances mitochondrial calcium and ROS production, which promotes myofibroblast transdifferentiation and HTS formation. Inhibition of the TRPC3-mediated Nox4/pSmad2/3 pathway may be a useful strategy to limit HTS formation after injury.β (TGF
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DOI：
10.4081/ejh.2013.e40
发表时间：
2013-12-04
期刊：
European journal of histochemistry : EJH
影响因子：
--
作者：
Latella G;Vetuschi A;Sferra R;Speca S;Gaudio E
通讯作者：
Gaudio E
影响因子：
6
作者：
Lakos, G;Takagawa, S;Varga, J
通讯作者：
Varga, J
DOI：
10.26355/eurrev_201812_16652
发表时间：
2018-12-01
影响因子：
3.3
作者：
Vetuschi, A.;Pompili, S.;Sferra, R.
通讯作者：
Sferra, R.
DOI：
10.1016/j.bbrc.2018.07.132
发表时间：
2018-09-10
影响因子：
3.1
作者：
Kheradpezhouh, Ehsan;Zhou, Fiona H.;Rychkov, Grigori Y.
通讯作者：
Rychkov, Grigori Y.
增强线粒体瞬时受体电位通道，高血压大鼠脉管系统中典型 3 型介导的钙处理。
影响因子：
5.4
作者：
Wang B;Xiong S;Lin S;Xia W;Li Q;Zhao Z;Wei X;Lu Z;Wei X;Gao P;Liu D;Zhu Z
通讯作者：
Zhu Z