Genetic or pharmacological reduction of cholangiocyte senescence improves inflammation and fibrosis in the Mdr2 ^-/-  mouse.

ABSTRACT:

Background & aims

Cholangiocyte senescence is important in the pathogenesis of primary sclerosing cholangitis (PSC). We found that CDKN2A (p16), a cyclin-dependent kinase inhibitor and mediator of senescence, was increased in cholangiocytes of patients with PSC and from a PSC mouse model (multidrug resistance 2; Mdr2 ^-/-). Given that recent data suggest that a reduction of senescent cells is beneficial in different diseases, we hypothesised that inhibition of cholangiocyte senescence would ameliorate disease in Mdr2 ^-/- mice.

Methods

We used 2 novel genetic murine models to reduce cholangiocyte senescence: (i) p16^Ink4a apoptosis through targeted activation of caspase (INK-ATTAC)xMdr2 ^-/-, in which the dimerizin

SUBMITTER: Alsuraih M 

PROVIDER: S-EPMC8044431 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature