Hydrogen Sulfide Diminishes Activation of Adventitial Fibroblasts Through the Inhibition of Mitochondrial Fission.
Hydrogen Sulfide Diminishes Activation of Adventitial Fibroblasts Through the Inhibition of Mitochondrial Fission.
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硫化氢通过抑制线粒体裂变减少外膜成纤维细胞的活化。
DOI：
10.1097/fjc.0000000000001250
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发表时间：
2022-06-01
影响因子：
3
通讯作者：
Li, Bao
中科院分区：
文献类型：
--
作者：
Lu, Zhao-Yang;Guo, Chun-Ling;Yang, Bin;Yao, Yao;Yang, Zhuo-Jing;Gong, Yu-Xin;Yang, Jing-Yao;Dong, Wen-Yuan;Yang, Jun;Yang, Hai-Bing;Liu, Hui-Min;Li, Bao
血管损伤时外膜成纤维细胞（AF）的激活有助于血管重塑。硫化氢（H2S）是一种气体信号分子，调节多种心血管功能。本研究旨在探讨外源性H2S是否能改善转化生长因子-β 1（TGF-β 1）诱导的AF活化，并探讨其分子机制。免疫荧光染色和western blot检测I型胶原和α-平滑肌肌动蛋白的表达。采用Kit-8细胞计数法和transwell法分别检测AFs的增殖和迁移情况。线粒体形态学采用MitoTracker Red染色。通过蛋白质印迹法（western blot）检测信号通路的激活情况。采用MitoSOX和JC-1（5，5 ′，6，6 ′-四氯-1，1，3，3 ′-四乙基苯并咪唑羰花青碘化物）染色法测定线粒体活性氧和线粒体膜电位。我们的研究表明，外源性H2S处理通过阻断动力蛋白相关蛋白1（Drp1）介导的线粒体分裂和调节线粒体活性氧的产生，显著抑制TGF-β 1诱导的AF增殖、迁移和表型转变。此外，外源性H2S通过调节Rho相关蛋白激酶1依赖的Drp1磷酸化来逆转TGF-β 1诱导的线粒体分裂和AF激活。总之，我们的研究结果表明，外源性H2S通过Rho相关蛋白激酶1依赖性方式抑制Drp1介导的线粒体分裂来减弱TGF-β 1诱导的AF激活。
Activation of adventitial fibroblasts (AFs) on vascular injury contributes to vascular remodeling. Hydrogen sulfide (H2S), a gaseous signal molecule, modulates various cardiovascular functions. The aim of this study was to explore whether exogenous H2S ameliorates transforming growth factor-β1 (TGF-β1)–induced activation of AFs and, if so, to determine the underlying molecular mechanisms. Immunofluorescent staining and western blot were used to determine the expression of collagen I and α-smooth muscle actin. The proliferation and migration of AFs were performed by using cell counting Kit-8 and transwell assay, respectively. The mitochondrial morphology was assessed by using MitoTracker Red staining. The activation of signaling pathway was evaluated by western blot. The mitochondrial reactive oxygen species and mitochondrial membrane potential were determined by MitoSOX and JC-1 (5,5′,6,6′-tetrachloro-1,1,3,3′-tetraethylbenzimidazolyl carbocyanine iodide) staining. Our study demonstrated exogenous H2S treatment dramatically suppressed TGF-β1–induced AF proliferation, migration, and phenotypic transition by blockage of dynamin-related protein 1 (Drp1)–mediated mitochondrial fission and regulated mitochondrial reactive oxygen species generation. Moreover, exogenous H2S reversed TGF-β1–induced mitochondrial fission and AF activation by modulating Rho-associated protein kinase 1–dependent phosphorylation of Drp1. In conclusion, our results suggested that exogenous H2S attenuates TGF-β1–induced AF activation through suppression of Drp1-mediated mitochondrial fission in a Rho-associated protein kinase 1–dependent fashion.