title: Hydrogen sulfide suppresses migration, proliferation and myofibroblast transdifferentiation of human lung fibroblasts.
abstract: We previously reported that hydrogen sulfide (H(2)S) was implicated in the pathogenesis of bleomycin-induced pulmonary fibrosis in rat, but the cellular mechanisms underlying the role it played were not well characterized. The present study was undertaken to investigate the role of the exogenous H(2)S in human lung fibroblast (MRC5) migration, proliferation and myofibroblast transdifferentiation induced by fetal bovine serum (FBS) and growth factors in vitro, to elucidate the mechanisms by which H(2)S inhibits pathogenesis of pulmonary fibrosis. We found that H(2)S incubation significantly decreased the MRC5 cell migration distance stimulated by FBS and basic fibroblast growth factor (bFGF), inhibited MRC5 cell proliferation induced by FBS and platelet-derived growth factor-BB (PDGF-BB), and also inhibited transforming growth factor-beta1 (TGF-beta1) induced MRC5 cell transdifferentiation into myofibroblasts. Moreover, preincubation with H(2)S decreased extracellular signal-regulated kinase (ERK1/2) phosphorylation in MRC5 cells induced by FBS, PDGF-BB, TGF-beta1, and bFGF. However, the inhibition effects of H(2)S on MRC5 cell migration, proliferation and myofibroblast transdifferentiation were not attenuated by glibenclamide, an ATP-sensitive K(+) channel (K(ATP)) blocker. Thus, H(2)S directly suppressed fibroblast migration, proliferation and phenotype transform stimulated by FBS and growth factors in vitro, which suggests that it could be an important mechanism of H(2)S-suppressed pulmonary fibrosis. These effects of H(2)S on pulmonary fibroblasts were, at least in part, mediated by decreased ERK phosphorylation and were not dependent on K(ATP) channel opening.
authors: Department of Geriatrics, Peking University First Hospital, Xishiku Street No. 8, West District, Beijing, People's Republic of China.
authors: Li-Ping
authors: LP
authors: Fang
authors: Qing
authors: Q
authors: Lin
authors: Chao-Shu
authors: CS
authors: Tang
authors: Xin-Min
authors: XM
authors: Liu
mesh_terms: D000393:Air Pollutants / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D054338:Cell Transdifferentiation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D054086:KATP Channels / Q000187:drug effects / Q000502:physiology; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D010766:Phosphorylation
chemical_list: D000393:Air Pollutants; D036341:Intercellular Signaling Peptides and Proteins; D054086:KATP Channels; D048049:Extracellular Signal-Regulated MAP Kinases; D006862:Hydrogen Sulfide