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MicroRNA-mRNA integral analysis in CD4+ T cell in primay biliary cholangitis (PBC)

ABSTRACT: microRNA-mRNA integral analysis in CD4+ T cell in primay biliary cholangitis (PBC)

PROVIDER: PRJNA360230 | ENA |

REPOSITORIES: ENA

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microRNA profile in CD4+ T cell in healthy control and Primay biliary cholangitis (PBC) [miRNA]

Project description:Primary biliary cholangitis (PBC), formally known as primary biliary cirrhosis, is an autoimmune liver disease of unknown pathogenesis. Consequently, therapeutic targets for PBC have yet to be identified. As CD4+ T cells play a pivotal role in immunological dysfunction observed in PBC, we analyzed microRNA(miRNA) and mRNA expression in CD4+ T cells to investigate PBC pathogenesis and identify novel therapeutic targets.

2017-01-06 | GSE93171 | GEO

mRNA profile in CD4+ T cell in healthy control and Primay biliary cholangitis (PBC) [mRNA]

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Bulk RNA-seq in cholangiocytes from mouse model of primary biliary cholangitis

Project description:Background & Aims: Late-stage primary biliary cholangitis (PBC) is defined by bile duct loss, ductular reaction, peribiliary inflammation and fibrosis. Loss of anion exchanger 2 (AE2), the ‘bicarbonate umbrella’ and ductulo-canalicular junctions (DCJ) are hypothesized to promote PBC progression. The secretin (Sct)/secretin receptor (SR) axis controls cystic fibrosis transmembrane receptor (CFTR) activation and AE2 opening, and controls choleresis. We aimed to define the impact of Sct/SR signaling on biliary secretory processes and subsequent injury in late-stage PBC mouse model and human samples. Methods: Female and male wild-type (WT) and dominant-negative transforming growth factor beta receptor II (dnTGFβRII, late-stage PBC model) at 32 wks of age were treated with Sct for 1 wk or 8 wks. Pathways mediated by Sct were identified by RNA-seq in isolated cholangiocytes. Sct/SR/CFTR/AE2 expression and MUC1 levels were evaluated in human control and late-stage PBC. Results: Biliary Sct, SR, CFTR and AE2 expression is reduced in late-stage PBC mouse models and human samples. Sct treatment decreased bile duct loss, ductular reaction, inflammation and fibrosis in late-stage PBC models, as well as hepatic bile acid release and DCJ formation. RNA-seq identified that Sct promoted mature epithelial cell marker expression, specifically anterior grade 2 (Agr2, expressed only in cholangiocytes). Late-stage PBC models and human samples had reduced biliary MUC1, which was enhanced with Sct treatment. Conclusion: Loss of the Sct/SR pathway in late-stage PBC results in a faulty ‘bicarbonate umbrella’ and reduced Agr2 and mucin production. Sct restores cholangiocyte secretory processes and DCJ formation through enhanced mature cholangiocyte phenotypes and healthy bile duct growth. The Sct/SR axis may be a therapeutic target for late-stage PBC patients.

2022-06-17 | GSE202676 | GEO

microRNA-mRNA integral analysis in CD4+ T cell in primay biliary cholangitis (PBC)

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-01-06 | GSE93172 | GEO

Bottom-up Proteomics of Saliva in Autoimmune Hepatitis and Primary Biliary Cholangitis

Project description:Autoimmune Hepatitis (AIH) and Primary Biliary Cholangitis (PBC) are autoimmune diseases that target the liver in which the immune system produces an inappropriate response to self-antigens resulting in inflammation, damage, and dysfunction of hepatic tissues. Despite progress in the understanding of the etiopathogenesis and in the diagnostic and therapeutic approach of these diseases, critical issues remain concerning the early diagnosis of affected individuals. The present study aims to detect and characterize by a gel-based bottom-up proteomic approach the acid-insoluble fraction of salivary proteome from patients affected by AIH and PBC with respect to healthy controls (HCs). The study was performed on the salivary acid-insoluble proteins after in-gel digestion starting from: i) the entire SDS-PAGE lane; ii) a portion of the SDS-PAGE at lowest molecular weight (MW </= 25 kDa).

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Common functional alterations identified in blood transcriptome of autoimmune cholestatic liver and inflammatory bowel diseases

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.

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Characterization of liver immune cell subsets of primary biliary cholangitis (PBC) mouse models using single-cell RNA sequencing

Project description:Characterization of liver immune cell subsets of primary biliary cholangitis (PBC) mouse models using single-cell RNA sequencing

| PRJNA773416 | ENA

Comparative analysis of liver tissues from heahtly mice and mice suffering from cholangitis

Project description:The goal of the study was to compare the transcriptomic signature (by bulk RNA-sequencing) of hepatic tissues of mice either healthy/normal or affected with primary sclerosing cholangitis (PSC) or primary biliary cholangitis mouse (PBC) (Paillet et al, J Exp Med, 2021). Transcriptomic analyses revealed mostly convergent alterations in the gene expression patterns when PBC and PSC were compared to normal, age- and sex-matched controls. Gene Ontology (GO) term analyses of the modulated mRNAs revealed a significant enrichment of genes involved in inflammation, immune response and chemotaxis of different leukocyte subsets . The expression of genes listed under the GO terms “inflammation” and “neutrophil” was not significantly different (p>0.5, Student t-test) between PBC and PSC. In sharp contrast, genes listed under the GO terms “T cell” and “B cell” were significantly (p<0.05, Student t-test) upregulated in PBC compared to PSC livers. Deeper analysis of the aforementioned liver RNA-seq dataset indicated that several genes specifically involved in Th1 and Tc1 responses were upregulated in PBC livers with respect to controls and, in some cases also with respect to PSC. Especially, this applies to Tc1-related genes encoding the markers CD8a, CD274 (best known as PD-L1), UL16 binding protein 1 (ULBP1), IFNγ, G Protein-Coupled Receptor 18 (GPR18), the transcription factor suppressor of cytokine signaling 1 (SOCS1), and the cytotoxic protease granzyme B (GzmB) (Paillet et al, J Exp Med, 2021).

2021-08-28 | GSE179993 | GEO

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

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.

2021-03-12 | GSE168758 | GEO

Characterization of liver immune cell subsets of primary biliary cholangitis (PBC) mouse models using single-cell RNA sequencing

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2021-10-25 | GSE186333 | GEO

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