Inhibition of microRNA-128-3p alleviates liver ischaemia-reperfusion injury in mice through repressing the Rnd3/NF-κB axis
Inhibition of microRNA-128-3p alleviates liver ischaemia-reperfusion injury in mice through repressing the Rnd3/NF-κB axis
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抑制 microRNA-128-3p 通过抑制 Rnd3/NF-kappa B 轴减轻小鼠肝脏缺血再灌注损伤
DOI：
10.1177/1753425920928449
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发表时间：
2020-06-02
期刊：
影响因子：
3.2
通讯作者：
Wu, Zhongjun
中科院分区：
文献类型：
--
作者：
Mou, Tong;Luo, Yunhai;Wu, Zhongjun
虽然肝缺血再灌注（I/R）损伤仍然是肝移植失败或移植后肝功能障碍的主要潜在原因，但其潜在机制仍然很难解释。微小RNA（miRNA）参与多种生理和病理过程，包括炎症。在此，我们发现miR-128- 3 p/Rho家族GT3（Rnd 3）/NF-κ B轴可能在肝脏I/R损伤中起关键作用。我们的研究结果表明，miR-128- 3 p的水平与Rnd 3水平在肝I/R期间呈负相关。双荧光素酶报告基因检测结果证明Rnd 3 mRNA是miR-128- 3 p的直接靶点。此外，Western blotting和定量RT-PCR分析显示，敲低miR-128- 3 p可上调Rnd 3 mRNA和蛋白水平，从而通过下调NF-κ B p65抑制NF-κ B B通路。因此，NF-κ B相关炎症因子和天冬氨酸转氨酶/丙氨酸转氨酶的血清水平降低。Rnd 3过表达可逆转miR-128- 3 p agomir诱导的NF-κ B B活化。总之，我们的研究结果表明，miR-128- 3 p的抑制可以通过miR-128- 3 p/Rnd 3/NF-κ B轴减轻肝脏I/R损伤，并可能促进新的保护性方法的开发，以对抗肝脏I/R损伤。
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-kappa 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-kappa B pathway through down-regulating NF-kappa B p65. Consequently, the serum levels of NF-kappa B-associated inflammatory factors and aspartate aminotransferase/alanine aminotransferase were decreased. Moreover, overexpression of Rnd3 could reverse the activation of NF-kappa 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-kappa B axis and may facilitate the development of novel protective approaches against liver I/R injury.