Hydrogen sulfide (H2S) has anti-fibrotic potential in lung, kidney and other organs. The exogenous H2S is released from sodium hydrosulfide (NaHS) and can influence the renal fibrosis by blocking the differentiation of quiescent renal fibroblasts to myofibroblasts. But whether H2S affects renal epithelial-to-mesenchymal transition (EMT) and the underlying mechanisms remain unknown. Our study is aimed at investigating the in vitro effects of H2S 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.
[1]Fudan Univ, Dept Pharmacol, Sch Pharm, Shanghai 201203, Peoples R China.
[2]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Nephrol, Shanghai 200062, Peoples R China.
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