P53-mediated regulation of bile acid disposition attenuates cholic acid-induced cholestasis in mice.

ABSTRACT:

Background and purpose

The tumour suppressor p53 is traditionally recognized as a surveillance molecule to preserve genome integrity. Recent studies have demonstrated that it contributes to metabolic diseases. Here, we investigated the role of p53 in the regulation of bile acid disposition and cholestasis.

Experimental approach

The bile acid disposition-related gene expression profile affected by p53 activation was assessed in mouse primary hepatocytes with p53 depletion and in Trp53-null mice. Dual luciferase reporter assay was used to detect the transcriptional activities of target genes. Anticholestatic effects of p53 activator doxorubicin were investigated in a 0.5% cholic acid-fed mouse model of cholestasis. Changes in bile acids were evaluated using metabolomics analys

SUBMITTER: Chen P 

PROVIDER: S-EPMC5715589 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature