Downregulation of miR‐497‐5p prevents liver ischemia‐reperfusion injury in association with MED1/TIMP‐2 axis and the NF‐κB pathway
Downregulation of miR‐497‐5p prevents liver ischemia‐reperfusion injury in association with MED1/TIMP‐2 axis and the NF‐κB pathway
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DOI：
10.1096/fj.202001029r
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发表时间：
2021-04
期刊：
影响因子：
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通讯作者：
Kun Wu;Guoquan Tao;Ting Xu;Yuanyuan An;Xiangyou Yu;Yi Wang;ShaoChuang Wang;Wen Guo;Long Ma
中科院分区：
文献类型：
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作者：
Kun Wu;Guoquan Tao;Ting Xu;Yuanyuan An;Xiangyou Yu;Yi Wang;ShaoChuang Wang;Wen Guo;Long Ma
肝脏缺血再灌注(I/R)损伤是肝移植中常见的临床病理现象。然而，其潜在的机制尚不完全清楚。MicroRNAs(MiRNAs)在肝脏I/R损伤中起重要作用。因此，对miRNAs功能的研究将有助于为肝脏I/R损伤的诊断提供新的生物标志物。本研究旨在评价miR-497-5P对小鼠肝脏I/R损伤的影响。通过生物信息学分析预测miR-497-5p在肝脏I/R损伤中的相关调控因子。采用血管结扎法建立肝脏I/R损伤动物模型。采用缺氧/复氧(H/R)方法建立体外模型。苏木精-伊红(HE)染色评价肝损伤程度。采用酶联免疫吸附试验(ELISA法)检测炎症因子。采用流式细胞仪检测细胞凋亡率。肝脏I/R损伤时miR-497b-5p表达增加。MiR-497b-5p基因敲除可抑制炎症因子的产生和细胞的凋亡。MED1和TIMP2过表达抑制细胞凋亡，减轻肝脏I/R损伤。MIR-497b-5p可通过抑制κ-2轴激活核因子-kappaB(NF-TIMP B)通路，促进肝脏I/R损伤。本研究可能为肝I/R损伤的治疗提供新的策略。
Liver ischemia‐reperfusion (I/R) injury is a common clinical pathological phenomenon, which is accompanied by the occurrence in liver transplantation. However, the underlying mechanism is not yet fully understood. MicroRNAs (miRNAs) play an important role in liver I/R injury. Therefore, the study of miRNAs function will contribute a new biological marker diagnosis of liver I/R injury. This study aims to evaluate effects of miR‐497‐5p in liver I/R injury in mice. The related regulatory factors of miR‐497‐5p in liver I/R injury were predicted by bioinformatics analysis. Vascular occlusion was performed to establish the liver I/R injury animal models. Hypoxia/reoxygenation (H/R) was performed to establish the in vitro models. Hematoxylin‐eosin (HE) staining was conducted to assess liver injury. The inflammatory factors were evaluated by enzyme‐linked immunosorbent assay (ELISA). Flow cytometry was adopted to assess the cell apoptosis. The expression of miR‐497b‐5p was increased in liver I/R injury. Knockdown of miR‐497b‐5p inhibited the production of inflammatory factors and cell apoptosis. Overexpression of mediator complex subunit 1 (MED1) and tissue inhibitor of metalloproteinase 2 (TIMP2) inhibited cell apoptosis to alleviate liver I/R injury. miR‐497b‐5p could activate the nuclear factor kappa‐B (NF‐κB) pathway by inhibiting the MED1/TIMP‐2 axis to promote liver I/R injury. This study may provide a new strategy for the treatment of liver I/R injury.