Upregulated microRNA‐450b‐5p represses the development of acute liver failure via modulation of liver function, inflammatory response, and hepatocyte apoptosis

Abstract

Abstract Objective It has been evidenced that microRNAs (miRs) exert crucial effects on acute liver failure (ALF), while the detailed function of miR‐450b‐5p in ALF progression remained obscure. The purpose of this research was to unravel the regulatory mechanism of miR‐450b‐5p in ALF via modulating Mouse Double Minute 2 protein (MDM2). Methods ALF was induced in mice by intraperitoneal injection of d‐galactosamine ( d‐GalN) and lipopolysaccharide (LPS). Adenoviruses containing overexpressed miR‐450b‐5p, MDM2 shRNA, and overexpressed MDM2 sequences were utilized to manipulate miR‐450b‐5p and MDM2 expression in the liver before the mice were treated with d‐GalN/LPS‐induced ALF. Subsequently, miR‐450b‐5p and MDM2 expression levels in liver tissues of ALF mice were examined. Serum biochemical parameters of liver function were tested, serum inflammatory factors were assessed, and the histopathological changes and hepatocyte apoptosis in liver tissues were observed. The relation between miR‐450b‐5p and MDM2 was verified. Results In ALF mice, miR‐450b‐5p was low‐expressed while MDM2 was high‐expressed. The upregulation of miR‐450b‐5p or downregulation of MDM2 could alleviate liver function, mitigate the serum inflammatory response and pathological changes in liver tissues, as well as inhibit the apoptosis of hepatocytes. MiR‐450b‐5p targeted MDM2. MDM2 overexpression reversed the repressive effects of elevated miR‐450b‐5p on ALF. Conclusion The upregulated miR‐450b‐5p blocks the progression of ALF via targeting MDM2. This study contributes to affording novel therapeutic targets for ALF treatment.

Keywords

• acute liver failure
• apoptosis
• inflammatory response
• microRNA‐450b‐5p
• Mouse Double Minute 2 protein
• pathological change