MicroRNA-125b protects liver from ischemia/reperfusion injury via inhibiting TRAF6 and NF-κB pathway
MicroRNA-125b protects liver from ischemia/reperfusion injury via inhibiting TRAF6 and NF-κB pathway
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MicroRNA-125b 通过抑制 TRAF6 和 NF-kappa B 通路保护肝脏免受缺血/再灌注损伤
DOI：
10.1080/09168451.2019.1569495
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发表时间：
2019-05-04
影响因子：
1.6
通讯作者：
Wu, Zhongjun
中科院分区：
文献类型：
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作者：
Huang, Zuotian;Zheng, Daofeng;Wu, Zhongjun
MicroRNA-125b (miR-125b)，先前被证明是多种疾病的潜在免疫调节剂，在本研究中减轻了小鼠肝脏缺血/再灌注（I/R）损伤。暴露于缺氧/再氧化（H/R）的RAW 264.7细胞中miR-125b降低。miR-125b过表达组血清和上清液中IL-1 β、IL-6和tnf - α的表达均降低。miR-125b agomir组肝脏组织病理学改变降低。在miR-125b拮抗剂组中，血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平与阴性对照组（NC）相比显著升高。上调miR-125b可抑制TNF受体相关因子6 （TRAF6）、IL-1 β的蛋白表达和p65的磷酸化（p-p65）。此外，通过免疫荧光测量，miR-125b抑制剂增强了p-p65的核易位。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kappa-轻链增强子（NF-kappa B）信号通路保护肝脏免受肝I/R损伤。
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-1 beta, IL-6 and TNF-alpha 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-1 beta 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-kappa B) signal pathway.