Studies On The Mechanism Of Hepatocyte MiR-30 In Suppressing Liver Fibrosis

Liver fibrosis showed a lot of hepatocyte apoptosis,necrosis and excessive deposition of extracellular matrix(ECM)on the organizational leve.It is the result of a variety of liver cells interaction.The hepatocytes which are the highest proportion in the liver are extremely sensitive against bacteria,viruses and toxic compounds.And then lead to a large number of hepatocytes apoptosis or necrosis,cause inflammation reaction of the liver tissue,which is the main factor to induce liver fibrosis/cirrhosis.TGF-β signaling pathway in this prosess is not only the key factor that induces hepatocytes apoptosis,but also a necessary condition for the occurrence of liver fibrosis.TGF-β signaling pathway is regulated at multiple levels,and it has always been a hot issue of cellular signal transduction research at home and abroad.In recent years,the research that microRNAs regulated TGF-P signaling pathway related cytokines,signal transduction protein and receptor has been paid more attention.KLF10 and KLF11,which are kown as TGF-β inducible early genes,can enhance TGF-β signaling pathways by inhibiting the expression of Smad7.We previously reported that miR-30 can regulate the TGF-P signaling by directly binding with the 3’UTR of KLF11 mRNA.We first detected the expression changes of miR-30 and KLF11,KLF10,Smad7 in CCl4-ind uced liver fibros is.We built the miR-30 recombinant adenovirus which can significantly improve the expression of miR-30 in hepatocyte.After the injection of recombinant adenovirus,the expression level of hepatocyte miR-30 significantly improved,KLF11 expression decreased,and hepatocyte apoptosis and liver inflammation also significantly lowered.Experiment in vitro also illustrates that miR-30 can inhibit the TGF-β signaling pathway in hepatocyte and significantly reduce profibrogenic factor expression by inhibiting the expression of KLF11 and significantly reduce TGF-β-induced apoptosis of hepatocytes.Furthermore,experiments in vivo and in vitro show that miR-30 in hepatocytes could significantly promote the proliferation of hepatocytes.Our study deeply analyses the mechanism of miR-30 to inhibit the action of the liver fibrosis,offers a new idea for the treatment of liver fibrosis.