| First Author | Hu S | Year | 2021 |
| Journal | Elife | Volume | 10 |
| PubMed ID | 34609282 | Mgi Jnum | J:312948 |
| Mgi Id | MGI:6792379 | Doi | 10.7554/eLife.71310 |
| Citation | Hu S, et al. (2021) beta-Catenin-NF-kappaB-CFTR interactions in cholangiocytes regulate inflammation and fibrosis during ductular reaction. Elife 10:e71310 |
| abstractText | 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 mouse knockouts of beta-catenin, one with beta-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 beta-catenin-positive hepatocytes and resolution of injury. KO1 showed persistent loss of beta-catenin, NF-kappaB activation in BECs, progressive DR and fibrosis, reminiscent of CF histology. We identify interactions of beta-catenin, NFkappaB, and CF transmembranous conductance regulator (CFTR) in BECs. Loss of CFTR or beta-catenin led to NF-kappaB activation, DR, and inflammation. Thus, we report a novel beta-catenin-NFkappaB-CFTR interactome in BECs, and its disruption may contribute to hepatic pathology of CF. |
