LncRNA 1700020I14Rik promotes AKR1B10 expression and activates Erk pathway to induce hepatocyte damage in alcoholic hepatitis

Yue Wu; Yabin Qi; Yangqiu Bai; Haihui Zhang; Wenliang Zhu; Shengli Zhou; Yanrui Zhang

doi:10.1038/s41420-022-01135-w

LncRNA 1700020I14Rik promotes AKR1B10 expression and activates Erk pathway to induce hepatocyte damage in alcoholic hepatitis

Cell Death Discov. 2022 Aug 26;8(1):374. doi: 10.1038/s41420-022-01135-w.

Authors

Yue Wu¹, Yabin Qi¹, Yangqiu Bai¹, Haihui Zhang¹, Wenliang Zhu², Shengli Zhou³, Yanrui Zhang⁴

Affiliations

¹ Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, Henan, China.
² Department of Critical Care Medicine, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, Henan, China.
³ Department of Pathology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, Henan, China.
⁴ Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, Henan, China. zzyanrui@sina.com.

Abstract

Alcoholic hepatitis (AH), a kind of alcoholic liver disease, shows poor prognosis. Long noncoding RNAs (lncRNAs) exert critical role in liver diseases. Here, we intended to investigate the possible molecular mechanism that 1700020I14Rik-based regulation of microRNA (miR)-137/Aldo-keto reductase family 1 member B10 (AKR1B10) affecting the inflammatory response and hepatocyte damage in AH. AH-related genes and the down-stream regulatory pathway were screnned by bioinformatics. Mouse normal hepatocyte cell line AML12 was selected to construct an ethanol-induced hepatocyte injury model for in vitro mechanistic validation, while we also established an AH mouse model using the ethanol with gradually increased concentration of 2-4% (v/v) for in vivo study. Specific role of 1700020I14Rik/miR-137/AKR1B10 in AML12 cell viability, proliferation and apoptotic capacity as well as inflammation and liver damage in mice were analyzed following ectopic and depletion approaches. We found elevated AKR1B10 and 1700020I14Rik but reduced miR-137 in AH. 1700020I14Rik was able to elevated miR-137-mediated AKR1B10. In vitro cell experiments and in vivo animal experiments validated that 1700020I14Rik reduced ethanol-induced hepatocyte damage and inflammation in AH mice through regulation of miR-137-mediated AKR1B10/Erk axis. The current study underlied that 1700020I14Rik could activate AKR1B10/Erk signaling through inhibition of miR-137, thereby promoting the hepatocyte damage in AH mice.