Impaired Intestinal Farnesoid X Receptor Signaling in Cystic Fibrosis Mice.

ABSTRACT:

Background & aims

The bile acid (BA)-activated farnesoid X receptor (FXR) controls hepatic BA synthesis and cell proliferation via the intestinal hormone fibroblast growth factor 19. Because cystic fibrosis (CF) is associated with intestinal dysbiosis, anomalous BA handling, and biliary cirrhosis, we investigated FXR signaling in CF.

Methods

Intestinal and hepatic expression of FXR target genes and inflammation markers was assessed in Cftr null mice and controls. Localization of the apical sodium-dependent BA transporter was assessed, and BAs in gastrointestinal tissues were analyzed. The CF microbiota was characterized and FXR signaling was investigated in intestinal tissue and organoids.

Results

Ileal murine fibroblast growth factor 19 ortholog (Fgf15) expression wa

SUBMITTER: Ikpa PT 

PROVIDER: S-EPMC6881665 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature