Gene-specific alterations of hepatic gene expression by ligand activation or hepatocyte-selective inhibition of retinoid X receptor-α signalling during inflammation.

ABSTRACT:

Background

Inflammation leads to transcriptional downregulation of many hepatic genes, particularly those activated by retinoid X receptor-α (RXRα) heterodimers. Inflammation-mediated reduction of nuclear RXRα levels is a main factor in reduced nuclear receptor (NR)-regulated hepatic gene expression, eventually leading to cholestasis and liver damage.

Aim

To investigate roles for RXRα in hepatic gene expression during inflammation, using two complementary mouse models: ligand activation of RXRα, and in mice expressing hepatocyte-specific expression of RXRα missing its DNA-binding domain (DBD; hs-RxrαΔex4(-/-) ).

Methods

To activate RXRα, mice were gavage-fed with LG268 or vehicle for 5 days. To inhibit RXRα function, hs-RxrαΔex4(-/-) mice were used. All mice were inje

SUBMITTER: Kosters A 

PROVIDER: S-EPMC3788689 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature