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

We previously reported that hydrogen sulfide (H2S) 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 H2S 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 H2S inhibits pathogenesis of pulmonary fibrosis. We found that H2S 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 H2S 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 H2S on MRC5 cell migration, proliferation and myofibroblast transdifferentiation were not attenuated by glibenclamide, an ATP-sensitive K+ channel (KATP) blocker. Thus, H2S 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 H2S-suppressed pulmonary fibrosis. These effects of H2S on pulmonary fibroblasts were, at least in part, mediated by decreased ERK phosphorylation and were not dependent on KATP channel opening.