Brg1-dependent epigenetic control of vascular smooth muscle cell proliferation by hydrogen sulfide
Brg1-dependent epigenetic control of vascular smooth muscle cell proliferation by hydrogen sulfide
复制标题
硫化氢对血管平滑肌细胞增殖的 Brg1 依赖性表观遗传控制
DOI：
10.1016/j.bbamcr.2013.03.002
复制
发表时间：
2013-06-01
影响因子：
5.1
通讯作者：
Jin, Hongfang
中科院分区：
文献类型：
--
作者：
Li, Li;Liu, Die;Jin, Hongfang
硫化氢(H_2S)对血管平滑肌细胞的增殖有调节作用。本研究旨在探讨硫化氢对血管平滑肌细胞增殖的表观遗传调控作用。基因芯片分析显示，硫化氢可显著下调内皮素-1刺激的增殖性血管平滑肌细胞中Brahma相关基因1(BRG1)和增殖细胞核抗原(PCNA)、神经营养素3(Ntf3)和血小板衍生生长因子A亚单位(PDGFα)的表达。BRG1是SWI/SNF装置(一种依赖于ATP的染色质重塑复合体)的中心催化亚基。BRG1的过表达和下调证实了BRG1在H_2S诱导的血管平滑肌细胞增殖抑制中起关键作用。荧光素酶报告实验、实时定量聚合酶链式反应和Western blotting结果表明，硫化氢抑制了BRG1的转录和表达。DNase I超敏分析显示，H_2S逆转了ET-1刺激的增殖细胞核抗原、Ntf3和PDGFα染色质重塑和血管平滑肌细胞的增殖。染色质免疫沉淀实验表明，H_2S抑制BRG1对增殖细胞核抗原、Ntf3和PDGFα启动子的募集。本研究结果表明，硫化氢通过抑制BRG1转录和表达的表观遗传学机制，以及通过减少BRG1在增殖细胞核抗原、Ntf3和PDGFα启动子区域的募集，来抑制血管平滑肌细胞的增殖。(C)2013爱思唯尔B.V.保留所有权利。
Hydrogen sulfide (H2S) can modulate the proliferation of vascular smooth muscle cells. This study was designed to investigate the epigenetic control of vascular smooth muscle cell proliferation in response to H2S. Microarray analysis indicated that Brahma-related gene 1 (Brg1) and proliferation-related genes including proliferating cell nuclear antigen (Pcna), neurotrophin 3 (Ntf3) and platelet-derived growth factor subunit A (Pdgf alpha) were significantly downregulated by H2S in endothelin-1-stimulated proliferative vascular smooth muscle cells. Brg1 is the central catalytic subunit of the SWI/SNF apparatus (an ATP-dependent chromatin remodeling complex). Overexpression and knockdown of Brg1 confirmed that Brg1 was crucial for H2S-induced inhibition of vascular smooth muscle cell proliferation. A luciferase reporter assay, real-time PCR and Western blotting demonstrated that H2S inhibited Brg1 transcription and expression. A DNase I hypersensitivity assay revealed that H2S reversed endothelin-1-stimulated Pcna, Ntf3 and Pdgf alpha chromatin remodeling and vascular smooth muscle cell proliferation. A chromatin immunoprecipitation assay indicated that H2S inhibited the recruitment of Brg1 to the Pcna, Ntf3 and Pdgf alpha promoters. The results of this study indicate that H2S inhibits vascular smooth muscle cell proliferation via an epigenetic mechanism involving the inhibition of Brg1 transcription and expression, and by reducing the recruitment of Brg1 to the Pcna, Ntf3 and Pdgf alpha promoter regions. (c) 2013 Elsevier B.V. All rights reserved.