Hydrogen sulfide suppresses migration, proliferation and myofibroblast transdifferentiation of human lung fibroblasts

Abstract

We previously reported that hydrogen sulfide (H 2S) 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 2S 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 2S inhibits pathogenesis of pulmonary fibrosis. We found that H 2S 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-β1 (TGF-β1) induced MRC5 cell transdifferentiation into myofibroblasts. Moreover, preincubation with H 2S decreased extracellular signal-regulated kinase (ERK1/2) phosphorylation in MRC5 cells induced by FBS, PDGF-BB, TGF-β1, and bFGF. However, the inhibition effects of H 2S on MRC5 cell migration, proliferation and myofibroblast transdifferentiation were not attenuated by glibenclamide, an ATP-sensitive K + channel (K ATP) blocker. Thus, H 2S 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 2S-suppressed pulmonary fibrosis. These effects of H 2S on pulmonary fibroblasts were, at least in part, mediated by decreased ERK phosphorylation and were not dependent on K ATP channel opening.