Hydrogen Sulfide Inhibits Transforming Growth Factor-[beta]1-Induced EMT via Wnt/Catenin Pathway

Hydrogen sulfide (H.sub.2 S) has anti-fibrotic potential in lung, kidney and other organs. The exogenous H.sub.2 S is released from sodium hydrosulfide (NaHS) and can influence the renal fibrosis by blocking the differentiation of quiescent renal fibroblasts to myofibroblasts. But whether H.sub.2 S affects renal epithelial-to-mesenchymal transition (EMT) and the underlying mechanisms remain unknown. Our study is aimed at investigating the in vitro effects of H.sub.2 S on transforming growth factor-[beta]1 (TGF-[beta]1)-induced EMT in renal tubular epithelial cells (HK-2 cells) and the associated mechanisms. The induced EMT is assessed by Western blotting analysis on the expressions of [alpha]-SMA, E-cadherin and fibronectin. HK-2 cells were treated with NaHS before incubating with TGF-[beta]1 to investigate its effect on EMT and the related molecular mechanism. Results demonstrated that NaHS decreased the expression of [alpha]-SMA and fibronectin, and increased the expression of E-cadherin. NaHS reduced the expression of TGF-[beta] receptor type I (T[beta]R I) and TGF-[beta] receptor type II (T[beta]R II). In addition, NaHS attenuated TGF-[beta]1-induced increase of [beta]-catenin expression and ERK phosphorylation. Moreover, it inhibited the TGF-[beta]1-induced nuclear translocation of [beta][beta]-catenin. These effects of NaHS on fibronectin, E-cadherin and T[beta]R I were abolished by the ERK inhibitor U0126 or [beta]-catenin inhibitor XAV939, or [beta]-catenin siRNA interference. We get the conclusion that NaHS attenuated TGF-[beta]1-induced EMT in HK-2 cells through both ERK-dependent and [beta]-catenin-dependent pathways.