Brg1-dependent epigenetic control of vascular smooth muscle cell proliferation by hydrogen sulfide

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• 作者：Li Li^a ; ¹ ; Die Liu^a ; ¹ ; Dingfang Bu^b ; Stella Chen^c ; Jianxin Wu^d ; Chaoshu Tang^e ; ^f ; ^{tangchaoshu@263.net.cn} ; Junbao Du^a ; ^f ; ^{junbaodu1@126.com} ; Hongfang Jin^a ; ^{jinhongfang51@126.com}
• 关键词：VSMCs ; vascular smooth muscle cells ; H2S ; hydrogen sulfide ; CSE ; cystathionine ¦Ã-lyase ; CBS ; cystathionine ¦Â-synthase ; MAPK ; mitogen-activated protein kinase ; Brg1 ; Brahma-related gene 1 ; Brm ; Brahma ; RNAi ; RNA interference ; RASMCs ; rat aortic smooth mu
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：1833
• 期：6
• 页码：1347-1355
• 全文大小：1170 K

文摘

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¦Á) 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¦Á 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¦Á 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¦Á promoter regions.