PI103 affects the progression of hepatic fibrosis through Ca 2+ and PI3K/Akt-dependent HSC apoptosis

Abstract

Activated hepatic stellate cell (HSC) is the central link to the occurrence and development of liver fibrosis, which can be reversed by promoting the apoptosis of HSC. The activation of HSC leads to an increase in proliferation, collagen synthesis and the contraction of HSCs. The studies in vitro and in vivo have shown that intracellular Ca2+ plays an important role in the mediating apoptosis and contraction of HSC. The phosphatidyl inositol 3-kinase (PI3K)/Akt signalling pathway is closely related to the occurrence and development of liver fibrosis. In this study, we investigated the effect of PI3K inhibitor PI103 on HSC stimulated by transforming growth factor-β1(TGF-β1) and explored its relevant mechanisms. The results showed PI3K inhibitor PI103 could inhibit the proliferation of activated HSC, increase its apoptosis, decrease intracellular Ca2+ concentration and reduce the expression of signal molecules PI3K and Akt and type I, III collagen as well. Our study demonstrates that Ca2+ and PI3K/Akt-dependent HSC apoptosis may serve as a potential novel target for anti-fibrosis therapy.