title: Brg1-dependent epigenetic control of vascular smooth muscle cell proliferation by hydrogen sulfide.
abstract: 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 (Pdgfα) 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 Pdgfα 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 Pdgfα 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 Pdgfα promoter regions.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Die
authors.initials: D
authors.lastname: Liu
authors.forename: Dingfang
authors.initials: D
authors.lastname: Bu
authors.forename: Stella
authors.initials: S
authors.lastname: Chen
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wu
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D057890:Epigenomics; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D020933:Neurotrophin 3; D009687:Nuclear Proteins; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D014157:Transcription Factors; C075278:platelet-derived growth factor A; D008156:Luciferases; C578929:Smarca4 protein, rat; D004265:DNA Helicases; D006862:Hydrogen Sulfide