Loss of Claudin-3 Impairs Hepatic Metabolism, Biliary Barrier Function, and Cell Proliferation in the Murine Liver
Felix Alexander Baier, Daniel Sánchez‐Taltavull, Tural Yarahmadov, Cristina Gómez, Fadi Jebbawi, Adrian Keogh, Riccardo Tombolini, Adolfo Odriozola, Mariana Castro Dias, Urban Deutsch, Mikio Furuse, Britta Engelhardt, Benoît Zuber, Alex Odermatt, Daniel Candinas, Deborah Stroka
Abstract
BACKGROUND & AIMS: Tight junctions in the liver are essential to maintain the blood-biliary barrier, however, the functional contribution of individual tight junction proteins to barrier and metabolic homeostasis remains largely unexplored. Here, we describe the cell type-specific expression of tight junction genes in the murine liver, and explore the regulation and functional importance of the transmembrane protein claudin-3 in liver metabolism, barrier function, and cell proliferation. METHODS: livers was assessed in young and aged mice by RNA sequencing (RNA-seq), and hepatic tissue was analyzed for lipid content and bile acid composition. A surgical model of partial hepatectomy was used to induce liver cell proliferation. RESULTS: mice after partial hepatectomy. CONCLUSIONS: Our data show that, in the liver, claudin-3 is necessary to maintain metabolic homeostasis, retention of bile acids, and optimal hepatocyte proliferation during liver regeneration. The RNA-seq data set can be accessed at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE159914.