肝细胞核因子4
下调和上调
再灌注损伤
医学
肝损伤
缺血
内科学
生物
转录因子
遗传学
基因
核受体
作者
Chaoqun Wang,Hongjun Yu,Shounan Lu,Shanjia Ke,Yanan Xu,Zhigang Feng,Bo Qian,Miaoyu Bai,Bing Yin,Xinglong Li,Yongliang Hua,Liqian Dong,Yao Li,Zhenan Bao,Zhongyu Li,Dong Chen,Bangliang Chen,Yongzhi Zhou,Shangha Pan,Yao Fu,Hongchi Jiang,Dawei Wang,Yong Ma
出处
期刊:Redox biology
[Elsevier]
日期:2022-11-01
卷期号:57: 102498-102498
被引量:4
标识
DOI:10.1016/j.redox.2022.102498
摘要
LncRNAs are involved in the pathophysiologic processes of multiple diseases, but little is known about their functions in hepatic ischemia/reperfusion injury (HIRI). As a novel lncRNA, the pathogenetic significance of hepatic nuclear factor 4 alpha, opposite strand (Hnf4αos) in hepatic I/R injury remains unclear. Here, differentially expressed Hnf4αos and Hnf4α antisense RNA 1 (Hnf4α-as1) were identified in liver tissues from mouse ischemia/reperfusion models and patients who underwent liver resection surgery. Hnf4αos deficiency in Hnf4αos-KO mice led to improved liver function, alleviated the inflammatory response and reduced cell death. Mechanistically, we found a regulatory role of Hnf4αos-KO in ROS metabolism through PGC1α upregulation. Hnf4αos also promoted the stability of Hnf4α mRNA through an RNA/RNA duplex, leading to the transcriptional activation of miR-23a and miR-23a depletion was required for PGC1α function in hepatoprotective effects on HIRI. Together, our findings reveal that Hnf4αos elevation in HIRI leads to severe liver damage via Hnf4αos/Hnf4α/miR-23a axis-mediated PGC1α inhibition.
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