Project description:Approximately 80% of patients with Primary Sclerosing Cholangitis (PSC) also have an underlying Inflammatory Bowel Disease (IBD). Notably, PSC-IBD presents a unique phenotype compared to Ulcerative Colitis or Crohn’s Disease alone , which may increase the risk of colitis-associated neoplasia. This case-control study comprises a cohort of 15 patients in the PSC-IBD group, 30 patients in the IBD-alone group, and 19 patients in the control group. Through the analysis of patient serum and colon tissue proteomics, colon gene expression, fecal gut microbiota, and in vitro data with human monocytes, we identified a specific interplay between systemic circulation and gut microbiota dysbiosis that may predispose PSC-IBD patients to neoplasia development. Our study revealed that PSC-IBD patients show a shift in gut microbiota towards an increase in Intestinibacter, a bacterium known to exacerbate IBD conditions.Interestingly, when comparing the PSC-IBD group to the IBD-alone group, we observed elevated miR-21 expression levels in fasting serum and stool samples. Finally, we partially reproduce the inflammatory PSC-IBD profile using miR-21 and bile acid GCDCA stimulus in human-derived monocytes. Our findings suggest that circulating miR-21, along with bile acid GCDCA, tissue macrophage recruitment, and distinct microbiota profiles, may contribute to the unique phenotype of IBD in PSC patients.
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.
2019-05-01 | GSE119600 | GEO
Project description:Dietary intervention on Primary Sclerosing Cholangitis
Project description:Cholestatic liver diseases, such as primary sclerosing cholangitis (PSC), are characterized by biliary fibroinflammation. Transforming growth factor-β (TGFβ) activated cholangiocytes release signals that recruit immune cells to drive inflammation and activate myofibroblasts to deposit the extracellular matrix (ECM). TGFβ signaling interacts with RUNX1 transcription factor. However, the role of RUNX1 has not been investigated in biliary fibroinflammation. Here we used mouse large biliary epithelial (MLE) cells that were treated with TGFβ (10ng/mL). ChIP-seq was performed followed by pathway analysis of genes associated with regions of RUNX1 binding.
2025-09-02 | GSE306786 | GEO
Project description:Gut viral community of primary sclerosing cholangitis murine model following colesevelam treatment
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:This study identified hepatic progenitor cell (HPC) niche-associated signalling pathways relevant in different chronic liver diseases using a high-throughput sequencing approach. The HPC niche was isolated using laser microdissection from patient samples diagnosed with hepatitis C virus (HCV) or primary sclerosing cholangitis (PSC), as models for hepatocellular or biliary regeneration. Differentially expressed genes in the HPC niche of PSC and HCV correlated to pathways involved in immune signalling, fibrogenesis and angiogenesis.
