Inhibition of microRNA-128-3p alleviates liver ischaemia-reperfusion injury in mice through repressing the Rnd3/NF-κB axis.
Tong MouYunhai LuoZuotian HuangDaofeng ZhengXingyu PuAi ShenJunliang PuTingting LiJiangwen DaiWei ChenZhongjun WuPublished in: Innate immunity (2020)
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.
Keyphrases
- signaling pathway
- oxidative stress
- lps induced
- pi k akt
- nuclear factor
- acute myocardial infarction
- inflammatory response
- mesenchymal stem cells
- brain injury
- crispr cas
- high resolution
- single cell
- skeletal muscle
- blood brain barrier
- south africa
- percutaneous coronary intervention
- amino acid
- protein protein
- high fat diet induced