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Ductular reaction-associated neutrophils promote biliary epithelium proliferation in chronic liver disease.


ABSTRACT:

Background & aims

Ductular reaction expansion is associated with poor prognosis in patients with advanced liver disease. However, the mechanisms promoting biliary cell proliferation are largely unknown. Here, we identify neutrophils as drivers of biliary cell proliferation and the defective wound-healing response.

Methods

The intrahepatic localization of neutrophils was evaluated in patients with chronic liver disease. Neutrophil dynamics were analyzed by intravital microscopy and neutrophil-labeling assays in DDC-treated mice. Neutrophil depletion or inhibition of recruitment was achieved using a Ly6g antibody or a CXCR1/2 inhibitor, respectively. Mice deficient in PAD4 (peptidyl arginine deiminase 4) and ELANE/NE (neutrophil elastase) were used to investigate the mechanism

SUBMITTER: Arino S 

PROVIDER: S-EPMC10585421 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature