GSTpi protects against angiotensin II-induced proliferation and migration of vascular smooth muscle cells by preventing signal transducer and activator of transcription 3 activation
GSTpi protects against angiotensin II-induced proliferation and migration of vascular smooth muscle cells by preventing signal transducer and activator of transcription 3 activation
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GSTpi 通过阻止信号转导器和转录激活剂 3 的激活来防止血管紧张素 II 诱导的血管平滑肌细胞增殖和迁移。
DOI：
10.1016/j.bbamcr.2013.11.024
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发表时间：
2014-02-01
影响因子：
5.1
通讯作者：
Luo, Lan
中科院分区：
文献类型：
--
作者：
Chen, Dan;Liu, Jinjiao;Luo, Lan
血管紧张素II（AngII）诱导的血管平滑肌细胞（VSMCs）过度增殖、肥大和迁移在动脉粥样硬化的发病机制中至关重要。谷胱甘肽S-转移酶pi（GSTpi）广泛存在于各种细胞中，对细胞的各种应激反应具有保护作用。然而，关于GSTpi在VSMCs中的作用的知识仍然有限。本研究探讨了GSTpi对血管紧张素Ⅱ诱导的VSMC增殖、肥大和迁移的影响及其可能机制。过表达和RNAi实验表明，GST pi抑制Ang Ⅱ诱导的VSMCs增殖、肥大和迁移，并使细胞周期由G 0/G1期阻滞于S期。免疫沉淀，质谱和共聚焦显微镜分析表明，GSTpi直接与信号转导和转录激活因子3（STAT 3），以防止Ang II触发的Src与STAT 3的结合，从而抑制Ang II刺激的磷酸化和STAT 3的核转位，以及细胞周期蛋白D1的表达。与此相反，GSTpi不影响Ang II激活的细胞外信号调节激酶（ERK 1/2）。GSTpi作为一种负调节因子，阻止血管紧张素II触发的VSMCs增殖信号，这表明它可以保护血管免受与动脉粥样硬化形成相关的压力。(C)2013爱思唯尔有限公司版权所有。
Angiotensin II (Ang II)-elicited excessive proliferation, hypertrophy and migration of vascular smooth muscle cells (VSMCs) are vital to the pathogenesis of atheroclerosis. Glutathione S-transferase pi (GSTpi) exists extensively in various kinds of cells and protects cells against different stresses. However, knowledge remains limited about what GSTpi acts in VSMCs. We investigated the effect of GSTpi on Ang II-induced VSMC proliferation, hypertrophy and migration and its latent mechanism. Overexpression and RNAi experiments demonstrated that GSTpi inhibited Ang II-induced proliferation, hypertrophy and migration of VSMCs and arrested progression of cell cycle from G0/G1 to S phase. Immunoprecipitation, mass spectrometry and confocal microscopy analyses showed that GSTpi directly associated with signal transducer and activator of transcription 3 (STAT3) to prevent Ang II-triggered binding of Src to STAT3 and thus suppressed Ang II-stimulated phosphorylation and nuclear translocation of STAT3, as well as cyclin D1 expression. In contrast, GSTpi didn't affect Ang II-activated extracellular signal-regulated kinase (ERK1/2). GSTpi acts as a negative regulator to prevent Ang II-triggered proliferative signaling in VSMCs, suggesting that it may protect vessels against the stresses associated with atherosclerosis formation. (C) 2013 Elsevier B.V. All rights reserved.