Objective: This study investigated the role of miR-214 in the hepatocyte apoptosis induced by hypoxia/reoxygenation (H/R) injury.
Materials and methods: In vivo hepatic ischemia/reperfusion (HIR) injury, mice model and in vitro HR model were established. miR-214, TRAF1, ASK1, and JNK expression levels were detected by qRT-PCR and western blot. The apoptosis of mouse hepatocyte AML12 was detected by flow cytometry analysis. The interaction between miR-214 and TRAF1 was confirmed by dual-luciferase reporter gene assay.
Results: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were elevated in HIR injury mice compared with sham mice. miR-214 expression was down-regulated in liver tissues of HIR and H/R-induced hepatocytes, whereas TRAF1, ASK1, and JNK expressions were up-regulated in HIR and H/R groups. H/R stimulation promoted the apoptosis of hepatocytes, and miR-214 overexpression inhibited the apoptosis of hepatocytes. Besides, TRAF1 was a target of miR-214 and negatively regulated by miR-214. miR-214/TRAF1 pathway involved in the modulation of H/R-induced apoptosis of hepatocytes. In vivo study proved miR-214 reduced hepatic injury of HIR mice.
Conclusion: miR-214 overexpression reduces hepatocyte apoptosis after HIR injury through negatively regulating TRAF1/ASK1/JNK pathway.
Keywords: Apoptosis; Hepatic ischemia/reperfusion injury; Hypoxia/reoxygenation; TRAF1; miR-214.