Loss of apical sodium bile acid transporter alters bile acid circulation and reduces biliary damage in cholangitis
Vik Meadows, Corinn Marakovits, Burcin Ekser, Debjyoti Kundu, Tianhao Zhou, Konstantina Kyritsi, Linh Pham, Lixian Chen, Lindsey Kennedy, Ludovica Ceci, Nan Wu, Guido Carpino, Wenjun Zhang, Abdulkadir Isidan, Alison Meyer, Travis Owen, Eugenio Gaudio, Paolo Onori, Gianfranco Alpini, Heather Francis
Abstract
We evaluated knockdown of the apical sodium bile acid transporter (ASBT) using Vivo-Morpholino in Mdr2KO mice. ASBT inhibition decreases primary sclerosing cholangitis (PSC) pathogenesis by reducing hepatic mast cell infiltration, altering bile acid species/cholehepatic shunt, and regulating gut inflammation/dysbiosis. Since a large cohort of PSC patients present with IBD, this study is clinically important. We validated findings in human PSC and PSC-IBD along with studies in novel human 3-D organoids formed from human PSC livers.