Biliary NF-κB-Inducing Kinase Promotes Ductular Reaction, Inflammation, and Fibrosis and Impedes Liver Disease Resolution.

ABSTRACT: NF-κB-inducing kinase (NIK) is selectively upregulated in cholangiocytes during chronic liver disease, but its role in disease progression is poorly understood. We here show that cholangiocyte-specific overexpression of NIK (NIK^Tg) exacerbates liver disease progression. NIK^Tg mice were generated using a CK19-CreERT/loxp system. NIK^Tg and wild-type control (NIK^Con) mice were treated with thioacetamide (TAA) or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to induce liver disease. In a separate cohort, mice were allowed a 2-week recovery period following 4 weeks of TAA administration. NIK was also ablated in human HuCC-T1 cholangiocyte cultures (HuCC-T1^NIK-/-), and either wild-type NIK or the NIK^G885R mutant (defective in ac

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12680040 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature