Regulation of intestinal senescence during cholestatic liver disease modulates barrier function and liver disease progression.

ABSTRACT:

Background & aims

Senescence has been reported to have differential functions in cholangiocytes and hepatic stellate cells (HSCs) during human and murine cholestatic disease, being detrimental in biliary cells and anti-fibrotic in HSCs. Cholestatic liver disease is associated with loss of intestinal barrier function and changes in the microbiome, the mechanistic cause of which is undetermined.

Methods

Intestinal samples were analysed from controls and patients with primary sclerosing cholangitis, as well as wild-type (WT) and p16-3MR transgenic mice. Cholestatic liver disease was induced by bile duct ligation (BDL) and DDC diet feeding. Fexaramine was used as an intestinal-restricted FXR agonist and antibiotics were given to eliminate the intestinal microbiome. Senescent cel

SUBMITTER: Moreno-Gonzalez M 

PROVIDER: S-EPMC11418120 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature