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KMID : 0311120210620050453
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Yonsei Medical Journal
2021 Volume.62 No. 5 p.453 ~ p.460
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miRNA- 125b Signaling Ameliorates Liver Injury Against Obstructive Jaundice-Induced Excessive Fibrosis in Experimental Rats
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Zhang Xingyuan
Zhang Fang
Zhang Changxi
Li Jie
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Abstract
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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.
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KEYWORD
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miR-125b, liver injury, bile duct ligation, endoplasmic reticulum
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