The Study Of The Regulation Molecular Mechanism Of HPO In Hepatic Stellate Cells

Liver fibrosis is a common pathological change of chronic liver disease, which had done serious harm to human health. Studies have showed that The activation of hepatic stellate cells is the cellular basis of hepatic fibrosis. In this study, we found that the HPO had the specific function that inhibit of the activation of hepatic stellate cells(HSCs).The activation and proliferation of HSCs and the synthesis and secretion of ECM were the central link in the development of liver fibrosis. The proliferation of activated HSCs is increased in liver fibrosis. The activated HSCs express a-smooth muscle actin (a-SMA), can express a variety of cytokines and receptors. Recent studies suggested that Leptin could stimulate the activation of HSCs. In this study, we found that the HPO shown anti-fibrotic activity. HPO could inhibit the expression of a-SMA in HSC-T6cells. The BRDU incorporation assay showed that the HPO can inhibit the proliferation of activated HSC-T6cells, but not significant change the cell cycle of HSC-T6cells, and also do not affect the apoptosis of HSC-T6cells. Then, we examined the changes of signal transduction pathway in activated HSC-T6cells. The activation and proliferation of HSCs is a key link of liver fibrosis, mitogen-activated protein kinases(MAPK) pathway is the one major signal transduction pathways which can cause HSCs activation and proliferation and lead to liver fibrosis,it is mainly consist of P38、extracellular signal-regulated kinase (ERK)、c-jun N-terminal Kinase(JNK) three signal pathways. HPO could inhibit the activation of the MAPK pathway in HSC-T6cells. By realtime-PCR, we found that HPO can inhibit the expression of transforming growth factor(TGF-β), Tissue inhibitor of matrix metalloproteinase(TIMP-1) and collagen-I in activated HSC-T6cells, and HPO could also increase the anti-fibrosis-related miRNA (miR-29family) in HSC-T6cells.The result showed that HPO has the effection of anti-hepatic fibrosis. The experiment revealed the molecular mechanism of HPO inhibiting the activated HSCs and lays the foundation for the application of anti-liver fibrosis.