β-Catenin-NF-κB-CFTR interactions in cholangiocytes regulate inflammation and fibrosis during ductular reaction
Year: 2021
Type: article
Abstract: Expansion of biliary epithelial cells (BECs) during ductular reaction (DR) is observed in liver diseases including cystic fibrosis (CF), and associated with inflammation and fibrosis, albeit without complete understanding of underlying mechanism. Using two different genetic knockouts of β-catenin, one with β-catenin loss is hepatocytes and BECs (KO1), and another with loss in only hepatocytes (KO2), we demonstrate disparate long-term repair after an initial injury by 2-week choline-deficient ethionine- supplemented diet. KO2 show gradual liver repopulation with BEC-derived β-catenin- positive hepatocytes, and resolution of injury. KO1 showed persistent loss of β-catenin, NF-κB activation in BECs, progressive DR and fibrosis, reminiscent of CF histology. We identify interactions of β-catenin, NFκB and CF transmembranous conductance regulator (CFTR) in BECs. Loss of CFTR or β-catenin led to NF-κB activation, DR and inflammation. Thus, we report a novel β-catenin-NFκB-CFTR interactome in BECs, and its disruption may contribute to hepatic pathology of CF.
Source: eLife
DOI: 10.7554/elife.71310
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: Delineating Molecular Mechanisms Underlying Liver Progenitor Cell-Driven Liver Regeneration, G2104767787, G2131291340, G284113647, Elucidating the role of β-catenin signaling in liver progenitor cell-mediated liver regeneration, G3838156259, G4488245257, G4745120820, G9000019890, G9000059376, G9000245759, G9000270492, G9000279742, G9000344944, Identifying therapeutic options for intrahepatic cholangiocarcinoma, Role of Wnt-Beta-catenin in liver development and metabolic zonation
OpenAlex ID: W3202973107