title: Hydrogen sulfide suppresses transforming growth factor-β1-induced differentiation of human cardiac fibroblasts into myofibroblasts.
abstract: In heart disease, transforming growth factor-β1 (TGF-β1) converts fibroblasts into myofibroblasts, which synthesize and secrete fibrillar type I and III collagens. The purpose of the present study was to investigate how hydrogen sulfide (H2S) suppresses TGF-β1-induced differentiation of human cardiac fibroblasts to myofibroblasts. Human cardiac fibroblasts were serum-starved in fibroblast medium for 16 h before exposure to TGF-β1 (10 ng mL(-1)) for 24 h with or without sodium hydrosulfide (NaHS, 100 µmol L(-1), 30 min pretreatment) treatment. NaHS, an exogenous H2S donor, potently inhibited the proliferation and migration of TGF-β1-induced human cardiac fibroblasts and regulated their cell cycle progression. Furthermore, NaHS treatment led to suppression of fibroblast differentiation into myofibroblasts, and reduced the levels of collagen, TGF-β1, and activated Smad3 in TGF-β1-induced human cardiac fibroblasts in vitro. We therefore conclude that H2S suppresses TGF-β1-stimulated conversion of fibroblasts to myofibroblasts by inhibiting the TGF-β1/Smad3 signaling pathway, as well as by inhibiting the proliferation, migration, and cell cycle progression of human cardiac myofibroblasts. These effects of H2S may play significant roles in cardiac remodeling associated with heart failure.
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, China.|Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: YouEn
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, China.
authors.forename: JiaNing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, China.
authors.forename: LiangJun
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. ge.junbo@zs-hospital.sh.cn.|Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. ge.junbo@zs-hospital.sh.cn.
authors.forename: JunBo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000166:cytology; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D013440:Sulfides; D053773:Transforming Growth Factor beta1; C025451:sodium bisulfide; D006862:Hydrogen Sulfide
keywords: human cardiac fibroblasts; hydrogen sulfide; myofibroblasts; transforming growth factor β1