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miRNA- 125b Signaling Ameliorates Liver Injury Against Obstructive Jaundice-Induced Excessive Fibrosis in Experimental Rats

Yonsei Medical Journal 2021년 62권 5호 p.453 ~ 460
Zhang Xingyuan, Zhang Fang, Zhang Changxi, Li Jie,
소속 상세정보
 ( Zhang Xingyuan ) - Shandong University Cheeloo College of Medicine Shandong Provincial Qianfoshan Hospital Department of Hepatobiliary Surgery
 ( Zhang Fang ) - Binzhou Medical University Hospital Nursing Department
 ( Zhang Changxi ) - Binzhou Medical University Hospital Department of Hepatobiliary Surgery
 ( Li Jie ) - Shandong University Cheeloo College of Medicine Shandong Provincial Qianfoshan Hospital Department of Hepatobiliary Surgery

Abstract


Purpose: Multiple pathways are involved in inducing liver fibrosis, which can damage the integrity of liver. Among them, miR-125b has been found to exert an activating action on hepatic stellate cells. Endoplasmic reticulum stress and autophagy lead to liver disorders. Here, we evaluated the therapeutic influence of miR-125b on the endoplasmic reticulum function in injured livers submitted to bile duct ligation.

Materials and Methods: For inducing injury, bile duct ligation was done on miR-125b transgenic rats (miR-125b-Tg) in wild type rats. The rat T-6 cells received transfection of miR-125b mimic and Tunicamycin. Protein expressions were observed by western blot analysis.

Results: Compared to wild type rats, liver-injured rats showed significant impairment of liver function as assessed by the total bilirubin levels. The miR-125b-Tg rats showed decrease in activity of aspartate transaminase and alanine transaminase. Liver tissues of miR-125b-Tg rats showed weaker fibrotic matrix formation. Upregulation of miR-125b decreased the bile duct ligation-mediated hepatic disturbances for the expressions of endoplasmic reticulum kinase, inositol-requiring kinase 1alpha, sXBP1, CHOP, LC3, p62, ULK, and caspase-3/-8/-9. T-6 cells transfected with miR-125b mimic and treated with Tunicamycin caused decrease in levels of cleaved caspase-3, sXBP1, CHOP, and LC3. The miR-125b signaling showed protective effect on the liver tissues subjected to injury and fibrosis histopathology.

Conclusion: This study demonstrates a novel insight into the miR125b-mediated stabilization of endoplasmic reticulum integrity, which slows the progression of injury-induced hepatic deterioration.

키워드

miR-125b; liver injury; bile duct ligation; endoplasmic reticulum

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