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: Li-Ping Fang, Qing Lin, Chao-Shu Tang, Xin-Min Liu
• Journal: Pharmacological research (Pharmacol Res) Vol. 61 Issue 4 Pg. 298-305 (Apr 2010) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 19913099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Ltd. All rights reserved.

Chemical References

• 2-(5-benzo(1,3)dioxol-5-yl-2-tert-butyl-3H-imidazol-4-yl)-6-methylpyridine hydrochloride
• Benzodioxoles
• Cadherins
• Imidazoles
• Pyridines
• SMAD2 protein, human
• SMAD3 protein, human
• Smad2 Protein
• Smad3 Protein
• Transforming Growth Factor beta1
• Vimentin
• Pinacidil
• Cystathionine gamma-Lyase
• Glyburide
• Hydrogen Sulfide

Topics

• Benzodioxoles (pharmacology)
• Cadherins (metabolism)
• Cell Line, Tumor
• Cell Transdifferentiation (drug effects)
• Cystathionine gamma-Lyase (metabolism)
• Drug Interactions
• Epithelial Cells (drug effects, metabolism)
• Glyburide (pharmacology)
• Humans
• Hydrogen Sulfide (antagonists & inhibitors, metabolism, pharmacology)
• Imidazoles (pharmacology)
• Phosphorylation (drug effects)
• Pinacidil (pharmacology)
• Pulmonary Alveoli (cytology, drug effects, metabolism)
• Pulmonary Fibrosis (metabolism)
• Pyridines (pharmacology)
• Smad2 Protein (antagonists & inhibitors, metabolism)
• Smad3 Protein (antagonists & inhibitors, metabolism)
• Transforming Growth Factor beta1 (antagonists & inhibitors, pharmacology)
• Vimentin (metabolism)