C-X-C motif chemokine ligand 1 induced by Hedgehog signaling promotes mouse extrahepatic bile duct repair after acute injury.

ABSTRACT:

Background and aims

In extrahepatic bile duct (EHBD) cholangiopathies, including primary sclerosing cholangitis, a reactive cholangiocyte phenotype is associated with inflammation and epithelial hyperproliferation. The signaling pathways involved in EHBD injury response are poorly understood. In this study, we investigated the role of Hedgehog (HH) signaling and its downstream effectors in controlling biliary proliferation and inflammation after EHBD injury.

Approach and results

Using mouse bile duct ligation as an acute EHBD injury model, we used inhibitory paradigms to uncover mechanisms promoting the proliferative response. HH signaling was inhibited genetically in Gli1^-/- mice or by treating wild-type mice with LDE225. The role of neutrophils was tested using

SUBMITTER: Mohamad Zaki NH 

PROVIDER: S-EPMC9790600 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature