Farnesoid X receptor (FXR) activation induces the antioxidant protein metallothionein 1 expression in mouse liver

Experimental Cell Research
Bing WangXiaoyan Zhang

Abstract

Farnesoid X receptor (FXR) is a metabolic nuclear receptor, which protects liver from many endogenous and exogenous injuries. Metallothioneins (MTs) belong to a low-molecular-weight protein family involved in metal homeostasis and the regulation of hepatic oxidative stress. In the present study, we aimed to investigate the effect of FXR on hepatic MT1 expression and the underlying mechanism. C57BL/6 mice or primary cultured mouse hepatocytes were treated with the synthetic FXR ligand GW4064 or natural ligand CDCA. RNA-Sequencing (RNA-seq) analysis was performed to identify gene expression profile in the livers of mice treated with GW4064. Real-time PCR and Western blot were applied to determine the expression of MT1 and other FXR target genes in the livers of mice and primary hepatocytes treated with GW4064 and CDCA. Cellular and subcellular locations of MT1 in the livers of mice treated with GW4064 were examined using immunohistochemistry assay. FXR small interfering RNAs (siRNA) was transfected to silence FXR. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were utilized to confirm the regulation of MT1 gene promoter activity by FXR. RNA-seq analysis revealed that GW4064 treatment significantly induced MT1...Continue Reading

Citations

Sep 12, 2020·Pflügers Archiv : European journal of physiology·Gulzar AlamXiaoyan Zhang
Nov 24, 2020·Oxidative Medicine and Cellular Longevity·Natalia Jimenez-Moreno, Jon D Lane
Apr 26, 2021·Pharmacology & Therapeutics·Nana YanFrank J Gonzalez

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