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H 2 S inhibits the activation of hepatic stellate cells and downregulates the expression of urotensin II
Author(s) -
Liu Yang,
Li Yiming,
Yang Wenbin,
Cao Gang
Publication year - 2013
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12002
Subject(s) - urotensin ii , hepatic stellate cell , apoptosis , cell growth , blot , medicine , endocrinology , chemistry , cell , receptor , microbiology and biotechnology , biology , biochemistry , gene
Aim H 2 S , a newly discovered signaling gasotransmitter, has been found involved in the pathogenesis of portal hypertension through the H 2 S / CSE system. Studies also showed that urotensin II ( UII ), a recently discovered most potent vasoconstrictor, played an important role in cirrhotic portal hypertension. Therefore, studies were conducted to explore the relationship between H 2 S and UII in cirrhosis. Methods In the present study, the changes in the expression levels of cystathionine‐γ‐lyase ( CSE ), UII , urotensin II receptor ( UT ), collagen I , collagen III , tissue inhibitor of metalloproteinase‐1 ( TIMP ‐1) and α‐smooth muscle actin (α‐ SMA ) were determined by fluorescence quantitative polymerase chain reaction after exposure of hepatic stellate cells to H 2 S . The influence of H 2 S on UII was examined by western blotting, and the relationship between H 2 S and UII was further confirmed by detection of cell proliferation and apoptosis.Results Studies have shown that increase in H 2 S concentration could reduce the expression of UII , UT , collagen I , collagen III , TIMP ‐1 and α‐ SMA without involvement of CSE . Moreover, the results of western blotting further proved that H 2 S inhibited the expression of UII . The examination of cell proliferation by 5‐ethynyl‐2′‐deoxyuridine assay suggests that H 2 S significantly inhibited the proliferation of LX ‐2 cells and the proliferation‐promoting effect of UII . Similarly, the examination of cell apoptosis revealed that H 2 S could promote LX ‐2 cell apoptosis and inhibit the apoptosis‐inhibiting effect of UII . Conclusion H 2 S suppresses fibrosis by inhibiting the activation of hepatic stellate cells and reducing the expression of UII .