Mast Cells Induce Ductular Reaction Mimicking Liver Injury in Mice Through Mast Cell-Derived Transforming Growth Factor Beta 1 Signaling.

ABSTRACT:

Background and aims

Following liver injury, mast cells (MCs) migrate into the liver and are activated in patients with cholestasis. Inhibition of MC mediators decreases ductular reaction (DR) and liver fibrosis. Transforming growth factor beta 1 (TGF-β1) contributes to fibrosis and promotes liver disease. Our aim was to demonstrate that reintroduction of MCs induces cholestatic injury through TGF-β1.

Approach and results

Wild-type, Kit^W-sh (MC-deficient), and multidrug resistance transporter 2/ABC transporter B family member 2 knockout mice lacking l-histidine decarboxylase were injected with vehicle or PKH26-tagged murine MCs pretreated with 0.01% dimethyl sulfoxide (DMSO) or the TGF-β1 receptor inhibitor (TGF-βRi), LY2109761 (10 μM) 3 days before sacrifice. Hepa

SUBMITTER: Kyritsi K 

PROVIDER: S-EPMC7864988 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature