Role of miRNA-4804-3p in liver injury of chronic hepatitis B through inhibit chemerin/chemokine-like receptor 1 mediated NF-κB signal pathway

Abstract

Abstract Objective: This study aimed to investigate the role of microRNA (miRNA)-4804-3p in liver injury during chronic hepatitis B virus(HBV) infection through inhibit chemerin/chemokine-like receptor 1(CMKLR1) mediated NF-κB signal pathway. Methods: miRNA-4804-3p, CMKLR1, extracellular signal regulated kinase (ERK), and nuclear factor kappa B (NF-κB) mRNA expression were detected by qPCR, western blot or immunohistochemistry (IHC). A mouse model of liver injury induced by concanavalin A was established and used for experiments in vivo. Results: Pearson correlation analysis showed a significantly negative correlation between the expression level of miRNA-4804-3p and CMKLR1 in PBMCs of patients with CHB. The miRNA-4804-3p was significantly negatively correlated with the level of alanine transaminase in patients with CHB. Previous our study have showed that the cytokine secretion of human monocyte lines could be inhibited by miRNA-4804-3p. The level of CMKLR1 gene, phosphorylated ERK (p-ERK) and NF-κB protein in cells transfected with miRNA-4804-3p mimics was significantly decreased compared with that of the negative control group. The levels of IL-2, IL-10, TNF-α and IFN-γ in cell culture supernatant were no significant difference between miRNA-4804-3p mimics+CMKLR1 knocdown group and negative control group. The level of AST after injection with agomiRNA-4804-3p significantly decreased compared with that of pre-injection. The amount of inflammation in liver tissue of mice injected with agomiRNA-4804-3p was significantly lower compared with that of the negative control group, but the amount of fibrosis had no significant alteration. Conclusions: miRNA-4804-3p may inhibit chemerin/CMKLR1–mediated NF-κB signal pathway and be involved in regulating liver inflammatory injury in CHB. This study might not only provide a new explanation for the pathogenesis of CHB, but also provide new potential molecular markers for the prevention and treatment of CHB.