Transcriptomics

Dataset Information

0

The G protein-coupled bile acid receptor TGR5 (Gpbar1) modulates endothelin-1 signalling in liver


ABSTRACT: TGR5 (Gpbar1) is a G protein-coupled receptor responsive to bile acids (BAs), which is expressed in different non-parenchymal cells of the liver, including biliary epithelial cells, liver-resident macrophages, sinusoidal endothelial cells (LSECs) and activated hepatic stellate cells (HSCs). Mice with targeted deletion of TGR5 are more susceptible towards cholestatic liver injury induced by cholic acid-feeding and bile duct ligation, resulting in a reduced proliferative response and increased liver injury. Conjugated lithocholic acid (LCA) represents the most potent TGR5 BA ligand and LCA-feeding has been used as a model to rapidly induce severe cholestatic liver injury in mice. Thus, TGR5 knockout (KO) mice and wildtype littermates were fed a diet supplemented with 1%LCA for 84 hours. Liver injury and gene expression changes induced by the LCA-diet revealed an enrichment of pathways associated with inflammation, proliferation and matrix remodelling. Knockout of TGR5 in mice caused upregulation of endothelin-1 (ET-1) expression in the livers. Analysis of TGR5-dependent ET-1 signalling in isolated LSECs and HSCs demonstrated that TGR5 activation reduces ET-1 expression and secretion from LSECs and triggers internalization of the ET-1 receptor in HSCs dampening ET-1 responsiveness. Thus, we identified two independent mechanisms by which TGR5 inhibits ET-1 signalling and modulates portal pressure.

ORGANISM(S): Mus musculus

PROVIDER: GSE139075 | GEO | 2019/11/19

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2010-10-20 | GSE18759 | GEO
2023-08-19 | GSE240733 | GEO
2011-06-09 | E-GEOD-29776 | biostudies-arrayexpress
2011-06-09 | GSE29776 | GEO
2015-12-21 | E-GEOD-66796 | biostudies-arrayexpress
2010-10-20 | E-GEOD-18759 | biostudies-arrayexpress
2016-03-02 | E-GEOD-68000 | biostudies-arrayexpress
2021-03-18 | GSE169072 | GEO
2020-06-16 | GSE152494 | GEO
2021-01-28 | PXD020988 | Pride