Inhibition of microRNA-128-3p alleviates liver ischaemia–reperfusion injury in mice through repressing the Rnd3/NF‐ <b>κ</b> B axis
Tong Mou, Yunhai Luo, Zuotian Huang, Daofeng Zheng, Xingyu Pu, Ai Shen, Junliang Pu, Tingting Li, Jiangwen Dai, Wei Chen, Zhongjun Wu
Abstract
Although liver ischaemia-reperfusion (I/R) injury remains the primary underlying reason for liver transplant failure or post-transplantation liver dysfunction, the underlying mechanism is still largely elusive. MicroRNAs (miRNA) are involved in multiple physiological and pathological processes, including inflammation. Here, we identified that the miR-128-3p/Rho family GTPase 3 (Rnd3)/NF-κB axis might play a critical role in liver I/R injury. Our results demonstrated that the level of miR-128-3p was negatively correlated with the Rnd3 level during liver I/R. Dual luciferase reporter assay results proved that Rnd3 mRNA was a direct target of miR-128-3p. Additionally, Western blotting and quantitative RT-PCR analyses revealed that knock-down of miR-128-3p could up-regulate Rnd3 mRNA and protein levels, thereby suppressing the NF-κB pathway through down-regulating NF-κB p65. Consequently, the serum levels of NF-κB-associated inflammatory factors and aspartate aminotransferase/alanine aminotransferase were decreased. Moreover, overexpression of Rnd3 could reverse the activation of NF-κB caused by miR-128-3p agomir during liver I/R injury. Overall, our study results suggest that repression of miR-128-3p can alleviate liver I/R injury through the miR-128-3p/Rnd3/NF-κB axis and may facilitate the development of novel protective approaches against liver I/R injury.