Restoration of Wnt/β-catenin signaling attenuates alcoholic liver disease progression in a rat model

Journal of Hepatology
Chiung-Kuei HuangMiran Kim

Abstract

Alcoholic liver disease (ALD) is characterized by the development of fatty liver, alcoholic hepatitis, fibrosis and cirrhosis. However, the underlying mechanism(s) associated with progression remains elusive. Pro-inflammatory cytokines have been implicated in ALD progression due to pro-apoptotic effects on hepatocytes. Wnt/β-catenin signaling recently has been shown to promote inflammation and apoptosis, suggesting that activation of this signaling pathway may modulate ALD progression. The current study was designed to test whether pharmacological activation of Wnt/β-catenin signaling altered ALD development and progression in a rat model. Adult male Long Evans rats were fed with isocaloric liquid diets containing 0% or 37% ethanol for 8 weeks, and also treated with Wnt agonist during the last 3 weeks of the feeding regimen. Liver and blood samples were subjected to histology, TUNEL assay, immunoblot analysis, real-time quantitative PCR, and alanine transaminase (ALT) assay. Wnt/β-catenin signaling was negatively correlated with Foxo3A expression and reduced steatosis, cellular injury and apoptosis in ALD rats. Mutation experiments demonstrated that Foxo3A was critical for modulating these effects. Activation of Wnt/β-catenin s...Continue Reading

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Citations

Jan 19, 2016·Frontiers in Pharmacology·Ralf Weiskirchen
Jun 7, 2018·Journal of Cellular and Molecular Medicine·Yoshifumi IwagamiChiung-Kuei Huang
Nov 20, 2018·Nature Reviews. Gastroenterology & Hepatology·Maria J PerugorriaJesus M Banales
Sep 7, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chengcheng JiChiung-Kuei Huang
Jun 5, 2019·International Journal of Molecular Sciences·Ling-Zu KongTaeho Kwon
Jul 5, 2019·Cancers·Wenhui WangChaoyong He
Sep 11, 2019·Liver International : Official Journal of the International Association for the Study of the Liver·Kangan TanYuan Hong
Jan 23, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dennis R WarnerIrina A Kirpich

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