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微小RNA-125b通过抑制TRAF6和NF-κB信号通路保护肝脏免受缺血/再灌注损伤。

MicroRNA-125b protects liver from ischemia/reperfusion injury via inhibiting TRAF6 and NF-κB pathway.

作者信息

Huang Zuotian, Zheng Daofeng, Pu Junliang, Dai Jiangwen, Zhang Yuchi, Zhang Wanqiu, Wu Zhongjun

机构信息

a Department of Hepatobiliary Surgery , The First Affiliated Hospital of Chongqing Medical University , Chongqing , China.

出版信息

Biosci Biotechnol Biochem. 2019 May;83(5):829-835. doi: 10.1080/09168451.2019.1569495. Epub 2019 Jan 27.

Abstract

MicroRNA-125b (miR-125b), which was previously proved to be a potential immunomodulator in various disease, attenuated mouse hepatic ischemia/reperfusion (I/R) injury in this study. miR-125b was decreased in RAW 264.7 cells exposed to hypoxia/reoxygenation (H/R). The expression of IL-1β, IL-6 and TNF-α in both serum and supernate were reduced in miR-125b over-expression groups. The hepatic histopathological changes were reduced in miR-125b agomir groups. In the miR-125b antagomir groups, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly elevated compared with negative control (NC) groups. The protein expression of TNF receptor-associated factor 6 (TRAF6), IL-1β and the phosphorylation of p65 (p-p65) were suppressed by the up-regulation of miR-125b. Furthermore, the nuclear translocation of p-p65, measured by immunofluorescence, was enhanced by the miR-125b inhibitors. In conclusion, our study indicates that miR-125b protects liver from hepatic I/R injury via inhibiting TRAF6 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signal pathway.

摘要

微小RNA-125b(miR-125b)先前已被证明在多种疾病中是一种潜在的免疫调节剂,在本研究中可减轻小鼠肝脏缺血/再灌注(I/R)损伤。在暴露于缺氧/复氧(H/R)的RAW 264.7细胞中,miR-125b水平降低。在miR-125b过表达组中,血清和上清液中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的表达均降低。在miR-125b激动剂组中,肝脏组织病理学变化减轻。在miR-125b拮抗剂组中,与阴性对照(NC)组相比,血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平显著升高。miR-125b的上调抑制了肿瘤坏死因子受体相关因子6(TRAF6)、IL-1β的蛋白表达以及p65的磷酸化(p-p65)。此外,通过免疫荧光检测发现,miR-125b抑制剂增强了p-p65的核转位。总之,我们的研究表明,miR-125b通过抑制TRAF6和活化B细胞核因子κB(NF-κB)信号通路保护肝脏免受肝I/R损伤。

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