Role Of MiR-506-3p/Nur77 Pathway In HBV Related Liver Fibrosis

Background:Liver fibrosis is a necessary stage for various chronic liver diseases to develop into cirrhosis and liver cancer.Studies have shown that hepatitis B virus(HBV)mediates inflammation or necrosis of hepatocytes through immune response,and the disease persists and reappears repeatedly,thus accelerating the process of liver fibrosis.In this study,miR-506-3p and Nur77 were used to investigate their mechanism of action in HBV-related liver fibrosis,providing a theoretical basis for the diagnosis and treatment of hepatitis B fibrosis in clinical practice.Methods:1.The effect of HBV on the expression of mRNA and protein of miR-506-3p,Nur77 and liver fibrosis-related genes(α-SMA,CoL1A1 and TIMP-1)was observed by transfecting HBV or blocking HBV replication in group experiments.2.The experiments were grouped according to the different plasmids.AD38 cells,HepG2-NTCP cells,and LX2 cells were transfected with miR-506-3p mimic or inhibitor,and pcDNA-3.1-Nur77 or Nur77 gRNA.The level of miR-506-3p,Nur77,and liver fibrosis related genes(α-SMA,CoL1A1,and TIMP-1)were detected by qPCR and western blotting respectively.Based on the relevant data results,the relationship between miR-506-3p/Nur77 and HBV related liver fibrosis was analyzed.3.28 patients with chronic hepatitis B diagnosed from 2017 to 2020 were included,and their clinical data,serum,and liver tissue pathological samples were collected.Liver tissue was stained with H&E and Masson’s,and liver fibrosis was evaluated using the METAVIR system.The difference of miR-506-3p in serum in different stages of liver fibrosis was detected by qPCR.Immunohistochemical staining was used to detect the expression of Nur77 protein in liver tissue.The relationship between miR-506-3p/Nur77 and Liver Fibrosis score was analyzed by correlation analysis.Results:1.HBV infection down-regulated the expression of miR-506-3p,while up-regulating the expression levels of Nur 77 and fibrosis genes such as α-SMA,CoL1A1 and TIMP-1 in hepatocytes.Blocking HBV showed the opposite trend to the above,and all differences were statistically significant(P<0.05).2.Overexpression of miR-506-3p inhibits Nur77 and LF-related gene expression(P<0.01).3.Overexpression of Nur77 enhances LF-related gene expression(P<0.01),but Nur77 did not affect miR-506-3p expression.4.Nur 77 expression in liver tissue was positively correlated with liver fibrosis(r=0.935,P<0.05),whereas serum miR-506-3p was significantly negatively correlated with liver fibrosis(r=-0.839,P<0.05).Conclusion:Our data suggest that miR-506-3p inhibits the progression of HBV related liver fibrosis,while Nur77 positively correlates with HBV related liver fibrosis.HBV-infected hepatocytes activate hepatic stellate cells and exacerbate liver fibrosis via the miR-506-3p/Nur77 pathway,which is expected to be a new target for therapy.