Upregulation of miR-142-5p induced by lipopolysaccharide contributes to apoptosis of hepatocytes and hepatic failure.

OBJECTIVE

This study was probed to uncover the mechanism of miR-142-5p in septic liver injury.

MATERIALS AND METHODS

In this study, in-vitro and in-vivo models of sepsis were used. For in-vitro sepsis model, hepatocyte cell line (L02 cells) was treated with LPS (lipopolysaccharide). Whereas for in-vivo sepsis model, cecal ligation and puncture were performed in mice. Mice were assigned into three groups: control, CLP (Cecal Ligation Puncture), CLP + miR-142-5p inhibitor group. Liver injury was assessed via H&E staining. IL-6, TNF-α, and IL-1β expressions were assayed through ELISA kits. C-caspase-9, C-caspase-3, ERK, p65, and IκBα expressions were determined via western blot and RT-qPCR. Apoptosis in LPS-induced L02 cells was detected by TUNEL staining.

RESULTS

Our results show that miR-142-5p exhibited perspicuous upregulation in CLP mice tissues and LPS-induced L02 cells. On the other hand, inhibition of miR-142-5p could promote LPS-induced L02 cell activity and reduce apoptosis and inflammation. In terms of molecular mechanism, downregulation of miR-142-5p could abate sepsis-mediated acute hepatic injury by targeting SOCS1, through ERK and NF-κB pathway.

CONCLUSIONS

Overall our results demonstrate that miR-142-5p inhibitors can mitigate septic liver injury by downregulating the inflammation and apoptosis via targeting SOCS1. Thus, miR-142-5p can serve a potential therapeutic target for sepsis mediated acute hepatic injury.