miR-155 Aggravates Liver Ischemia/reperfusion Injury by Suppressing SOCS1 in Mice

Liver ischemia/reperfusion injury (IRI) occurs during partial liver resection and liver transplantation. Activation of Toll-like receptors (TLRs) is a key event triggered by a range of proinflammatory cytokines during liver I/R. Although it has been reported that miR-155 takes part in both innate and adaptive immune responses, the potential role of miR-155 in liver IRI remains unknown. In this study, we found that expression of miR-155 was upregulated during liver I/R by many inflammatory cytokines, and forced expression of miR-155 aggravated hepatocyte injury following liver I/R both in vivo and in vitro. Mice transfected with Ago-miR-155-a chemically modified miR-155-showed enhanced liver severity compared to those transfected with negative control miRNA by inhibiting the expression of SOCS1, the target of miR-155. Thus by the inhibition of SOCS1, the overexpression of miR-155 promoted activation of NF-κB, and elevating the production of proinflammatory cytokines, such TNF-α and IL-6. In conclusion, miR-155 aggravates liver I/R injury in vivo and hepatocyte hypoxia/reoxygenation injury by suppressing the expression of SOCS1.