title: Hydrogen Sulfide Inhibits Transforming Growth Factor-β1-Induced EMT via Wnt/Catenin Pathway.
abstract: 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-β1 (TGF-β1)-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 α-SMA, E-cadherin and fibronectin. HK-2 cells were treated with NaHS before incubating with TGF-β1 to investigate its effect on EMT and the related molecular mechanism. Results demonstrated that NaHS decreased the expression of α-SMA and fibronectin, and increased the expression of E-cadherin. NaHS reduced the expression of TGF-β receptor type I (TβR I) and TGF-β receptor type II (TβR II). In addition, NaHS attenuated TGF-β1-induced increase of β-catenin expression and ERK phosphorylation. Moreover, it inhibited the TGF-β1-induced nuclear translocation of ββ-catenin. These effects of NaHS on fibronectin, E-cadherin and TβR I were abolished by the ERK inhibitor U0126 or β-catenin inhibitor XAV939, or β-catenin siRNA interference. We get the conclusion that NaHS attenuated TGF-β1-induced EMT in HK-2 cells through both ERK-dependent and β-catenin-dependent pathways.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, 826 Zhangheng Road, Pudong New District, Shanghai, 201203, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lan
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, 826 Zhangheng Road, Pudong New District, Shanghai, 201203, China.
authors.forename: Hongya
authors.initials: H
authors.lastname: Hei
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, 826 Zhangheng Road, Pudong New District, Shanghai, 201203, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, 826 Zhangheng Road, Pudong New District, Shanghai, 201203, China.
authors.forename: Wanma
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, 826 Zhangheng Road, Pudong New District, Shanghai, 201203, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D051176:beta Catenin; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide