Project description:Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are heterogeneous chronic autoimmune diseases that may share underlying pathogenic mechanisms. Herein, we compared simultaneously analyzed blood transcriptomes from patients with PBC, PSC, and IBD.
Project description: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.
Project description:Mutations in GPR35 (G protein coupled receptor 35) are linked to ulcerative colitis and primary sclerosing cholangitis. How GPR35, which interacts with the Na/K-ATPase to determine ion transport, influences the transcriptome of macrophages and the ileum is unknown. Here compare transcript expression in bone marrow-derived macrophages and isolated ileum from mice deficient in GPR35 (knockout) with wild type mice by bulk RNA sequencing.
Project description:Cholangiocarcinoma (CCA) is a dreaded complication of primary sclerosing cholangitis (PSC), difficult to diagnose and associated with high mortality. Lack of animal models of CCA recapitulating the hepatic microenvironment of sclerosing cholangitis hinders development of novel treatments. We have developed and characterized a new mouse model of PSC-CCA through hydrodynamic tail vein injection of oncogenes pT3-EF1a-HA-myrAKT (AKT) and pT3-EF1a-YapS127A (YAP1), termed SB CCA.Mdr2-/-, which features reliable tumor induction in PSC-like background of biliary injury and fibrosis. To unravel the potential molecular profile of CCA developed in different liver context, we profiled the transcriptomes of tumor-bearing fibrotic (Mdr2-/-) (n = 6) and tumor-bearing wild-type liver tissues (n = 6) and compared to corresponding control nontumor-bearing fibrotic (Mdr2-/-) (n = 6) and healthy liver tissues (n = 6). RNA-seq analysis revealed profound transcriptional differences in CCA evolving in PSC-like context, compared to CCA in healthy liver.
