Impact of hypoxia and AMPK on CFTR-mediated bicarbonate secretion in human cholangiocyte organoids
Floris J.M. Roos, Marcel J. C. Bijvelds, Monique M.A. Verstegen, Henk P. Roest, Herold J. Metselaar, Wojciech G. Polak, Hugo R. de Jonge, Jan N.M. IJzermans, Luc J. W. van der Laan
2021American Journal of Physiology-Gastrointestinal and Liver Physiology15 citationsDOIOpen Access PDF
Abstract
The previously described liver-derived organoids resemble primary cholangiocytes and should be properly named intrahepatic cholangiocyte organoids (ICOs). ICOs have functional cholangiocyte ion channels (CFTR and ANO1). CFTR might be able to secrete bicarbonate directly into the bile duct lumen. Hypoxia inhibits CFTR and ANO1 functionality in ICOs, which can partially be restored by addition of an AMP kinase inhibitor. Hypoxia impairs cholangiocyte resistance against cytotoxic effects of bile, resulting in increased cell death.
Topics & Concepts
CholangiocyteOrganoidHypoxia (environmental)SecretionBicarbonateAMPKCell biologyChemistryInternal medicineBiologyMedicineProtein kinase AKinaseOxygenOrganic chemistryPancreatic function and diabetesNeonatal Respiratory Health ResearchFibroblast Growth Factor Research