microRNA-103a-3p promotes inflammation and fibrosis in nonalcoholic fatty liver disease by targeting HBP1.

BACKGROUND

As a metabolic-associated disease, nonalcoholic fatty liver disease (NAFLD) development is tightly linked to lipid accumulation, inflammatory response, and fibrosis. Our study was intended to expound the role of microRNA (miR)-103a-3p in the pathogenesis of NAFLD.

METHODS

First, potentially relevant genes in NAFLD were screened using microarray analysis. The expression of lipid metabolism-related, inflammatory, and liver fibrosis indicators in the serum of patients with NAFLD was analyzed. We established a NAFLD mouse model and analyzed the serum level of lipid metabolism- and inflammation-related factors and fibrosis in the liver tissues of NAFLD mice. The targeting relationship between miR-103a-3p and HBP1 was examined by dual-luciferase reporter gene assay, RT-qPCR, and Western blot. Finally, the simultaneous effects of miR-103a-3p and HBP1 knockdown on lipid metabolism, inflammatory response, and liver fibrosis in NAFLD mice were analyzed by rescue experiments.

RESULTS

MiR-103a-3p was upregulated in the serum of NAFLD patients and liver tissues of NAFLD mice, with increased lipid accumulation, inflammation, and liver fibrosis. HBP1 was reduced in liver tissues of NAFLD mice, and miR-103a-3p bound to and negatively regulated HBP1. Inhibition of miR-103a-3p or promotion of HBP1 improved liver function, decreased lipid accumulation, suppressed inflammatory response, and reduced liver fibrosis in NAFLD mice. Moreover, sh-HBP1 partially reversed the effect of miR-103a-3p inhibitor on NAFLD mice, leading to increased lipid accumulation, elevated inflammation, and fibrosis in the liver of mice.

CONCLUSIONS

miR-103a-3p inhibits the expression of HBP1, thus suppressing lipid metabolism, stimulating inflammatory responses, and promoting liver fibrosis in NAFLD.