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Inhibition of microRNA-128-3p alleviates liver ischaemia-reperfusion injury in mice through repressing the Rnd3/NF-?B axis.


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-?B 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-?B pathway through down-regulating NF-?B p65. Consequently, the serum levels of NF-?B-associated inflammatory factors and aspartate aminotransferase/alanine aminotransferase were decreased. Moreover, overexpression of Rnd3 could reverse the activation of NF-?B 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-?B axis and may facilitate the development of novel protective approaches against liver I/R injury.

SUBMITTER: Mou T 

PROVIDER: S-EPMC7491242 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Inhibition of microRNA-128-3p alleviates liver ischaemia-reperfusion injury in mice through repressing the Rnd3/NF-<b>κ</b>B axis.

Mou Tong T   Luo Yunhai Y   Huang Zuotian Z   Zheng Daofeng D   Pu Xingyu X   Shen Ai A   Pu Junliang J   Li Tingting T   Dai Jiangwen J   Chen Wei W   Wu Zhongjun Z  

Innate immunity 20200602 6


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  ...[more]

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