biostudies-literatureWang YNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSMichigan Metabolomics and Obesity CenterUniversity of Michigan Center for Gastrointestinal ResearchMichigan Diabetes Research and Training Centere71318https://www.ebi.ac.uk/biostudies/studies/S-EPMC12680040biostudies-literatureUnknown39(23)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 acFASEB journal : official publication of the Federation of American Societies for Experimental BiologyBiliary NF-κB-Inducing Kinase Promotes Ductular Reaction, Inflammation, and Fibrosis and Impedes Liver Disease Resolution.PMC12680040R01 DK114220DK089503R01 DK141559NIDDK P30DK034933NIH DK020572R01 DK130111Kang QRui LNikooie RWang YfalseBiliary NF-κB-Inducing Kinase Promotes Ductular Reaction, Inflammation, and Fibrosis and Impedes Liver Disease Resolution.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 ac2025-01-01T00:00:00Z2025 Dec2026-06-05T22:26:52.762Z2026-05-22T03:15:23.87ZS-EPMC126800404134843010.1096/fj.202502014RRR