Downregulation of TGR5 (GPBAR1) in biliary epithelial cells is characteristic of sclerosing cholangitis and may contribute to disease pathogenesis

Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation and progressive fibrosis of the biliary tree. The bile acid receptor TGR5 is found on biliary epithelial cells (BECs), where it promotes secretion, proliferation and tight junction integrity. Thus, we speculated that changes in TGR5 expression in BECs may contribute to PSC pathogenesis. Overall design: PSC mouse models with genetic background Abcb4-/-, Abcb4-/-/Tgr5Tg and wt mice were generated (N=4 per group). Liver bile ducts enriched on BECs by FACS sorting with EpCAM were isolated. BEC gene expression was analysed by single cell transcriptomics (scRNAseq) from the different mouse models.