title: Hydrogen sulfide attenuates epithelial-mesenchymal transition of human alveolar epithelial cells.
abstract: We previously reported that the endogenous cystathionine gamma-lyase (CSE)/hydrogen sulfide (H(2)S) pathway is implicated in the pathogenesis of bleomycin-induced pulmonary fibrosis in rats, but the exact cellular mechanisms are not well characterized. Epithelial-mesenchymal transition (EMT), induced by transforming growth factor beta1 (TGF-beta1) in alveolar epithelial cells, plays an important role in the pathogenesis of pulmonary fibrosis. We studied whether H(2)S could attenuate EMT in cultured alveolar epithelial cells and TGF-beta1 treatment suppressed CSE expression in A549 cells. Inhibition of endogenous CSE by dl-propargylglycine led to spontaneous EMT, as manifested by decreased E-cadherin level, increased vimentin expression and fibroblast-like morphologic features. Exogenous H(2)S applied to TGF-beta1-treated A549 cells decreased vimentin expression, increased E-cadherin level and retained epithelial morphologic features. In addition, preincubation with H(2)S decreased Smad2/3 phosphorylation in A549 cells stimulated by TGF-beta1, and H(2)S-inhibited alveolar EMT was mimicked by treatment with SB505124, a Smad2/3 inhibitor, but not pinacidil, an ATP-sensitive K(+) channel (K(ATP)) opener. H(2)S serves a critical role in preserving an epithelial phenotype and in attenuating EMT in alveolar epithelial cells, mediated, at least in part, by decreased Smad2/3 phosphorylation and not dependent on K(ATP) channel opening.
authors.affiliation: Department of Geriatrics, Peking University First Hospital, Xishiku Street No. 8, West District, Beijing, People's Republic of China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Fang
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Liu
mesh_terms: D052117:Benzodioxoles / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D054338:Cell Transdifferentiation / Q000187:drug effects*; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D004347:Drug Interactions; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D006862:Hydrogen Sulfide / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D020110:Pinacidil / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051899:Smad2 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
chemical_list: C519132:2-(5-benzo(1,3)dioxol-5-yl-2-tert-butyl-3H-imidazol-4-yl)-6-methylpyridine hydrochloride; D052117:Benzodioxoles; D015820:Cadherins; D007093:Imidazoles; D011725:Pyridines; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D020110:Pinacidil; D003542:Cystathionine gamma-Lyase; D005905:Glyburide; D006862:Hydrogen Sulfide