Exogenous H2S modulates mitochondrial fusion-fission to inhibit vascular smooth muscle cell proliferation in a hyperglycemic state.
Exogenous H2S modulates mitochondrial fusion-fission to inhibit vascular smooth muscle cell proliferation in a hyperglycemic state.
复制标题
外源性 H2S 调节线粒体融合裂变，抑制高血糖状态下血管平滑肌细胞增殖
DOI：
10.1186/s13578-016-0102-x
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发表时间：
2016
影响因子：
7.5
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Sun A;Wang Y;Liu J;Yu X;Sun Y;Yang F;Dong S;Wu J;Zhao Y;Xu C;Lu F;Zhang W
血管平滑肌细胞（VSMC）对高血糖的反应性增殖是动脉血管增生的重要过程。线粒体的形态变化是动态的，与分裂融合密切相关。硫化氢（H2S）被证实具有抗氧化、抗炎和抗增殖作用。然而，它对高血糖诱导的线粒体形态的影响知之甚少。本研究的目的是证明，H2S抑制VSMC增殖通过调节线粒体fisting.Methods和resultsWe观察较低的H2S水平，以及较高的增殖细胞核抗原（PCNA）和细胞周期蛋白D1和较高的线粒体融合分裂蛋白的表达水平，动力蛋白相关蛋白1（Drp 1）在人肾动脉和db/db小鼠主动脉。外源性H2S（100 μM NaHS）可抑制高糖诱导的人肺主动脉血管平滑肌细胞（HPASMC）增殖和迁移，降低增殖蛋白（PCNA和cyclin D1）的表达，减少细胞质和线粒体中ROS的产生。当HPASMCs增殖与高糖治疗，线粒体成为一个短的棒状结构的小球，而NaHS，线粒体分裂抑制剂和siDrp防止VSMC增殖，并保持线粒体作为固定和随机分散与fixedstructure.ConclusionExogenousH2S艾滋病抑制线粒体碎片化和影响增殖db/db小鼠和HPASMCs通过降低Drp 1的表达。
AimVascular smooth muscle cell (VSMC) proliferation in response to hyperglycemia is an important process in the development of arterial vessel hyperplasia. The shape change of mitochondria is dynamic and closely related to fission and fusion. Hydrogen sulfide (H2S) was confirmed to have anti-oxidative, anti-inflammatory and anti-proliferative effects. However, little it is known about its effects on mitochondrial morphology induced by hyperglycemia. The aim of the study is to demonstrate that H2S inhibits VSMC proliferation through regulating mitochondrial fission.Methods and resultsWe observe lower H2S levels as well as higher proliferative protein expression levels for proliferative cell nuclear antigen (PCNA) and cyclin D1 and higher mitochondrial fusion–fission protein expression levels for dynamin-related protein 1 (Drp 1) in human kidney arteries and in db/db mouse aorta. Exogenous H2S (100 μM NaHS) inhibits vascular smooth muscle cells of human pulmonary aorta(HPASMC) proliferation and migration in response to high glucose using the BrdU and scratch wound repair assays, decreases proliferative protein (PCNA and cyclin D1) expression, and reduces ROS production in the cytoplasm and mitochondria. When HPASMCs proliferate with a high glucose treatment, the mitochondria become small spheres with a short rod-shaped structure, whereas NaHS, a mitochondrial division inhibitor and siDrp prevent VSMC proliferation and maintain mitochondria as stationary and randomly dispersed with fixed structures.ConclusionExogenous H2S aids in inhibiting mitochondrial fragmentation and affects proliferation in db/db mice and HPASMCs by decreasing Drp 1 expression.