H2S inhibits the activation of hepatic stellate cells and downregulates the expression of urotensin II

Abstract

H2 S, a newly discovered signaling gasotransmitter, has been found involved in the pathogenesis of portal hypertension through the H2 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 H2 S and UII in cirrhosis. 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 H2 S. The influence of H2 S on UII was examined by western blotting, and the relationship between H2 S and UII was further confirmed by detection of cell proliferation and apoptosis. Studies have shown that increase in H2 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 H2 S inhibited the expression of UII. The examination of cell proliferation by 5-ethynyl-2'-deoxyuridine assay suggests that H2 S significantly inhibited the proliferation of LX-2 cells and the proliferation-promoting effect of UII. Similarly, the examination of cell apoptosis revealed that H2 S could promote LX-2 cell apoptosis and inhibit the apoptosis-inhibiting effect of UII. H2 S suppresses fibrosis by inhibiting the activation of hepatic stellate cells and reducing the expression of UII.