Gene expression profiles of peripheral blood mononuclear cells in primary biliary cirrhosis

摘要

Previous studies on gene expression profiles in primary biliary cirrhosis (PBC) have exclusively focused on liver tissue or intrahepatic cells. Since the pathological process is systemic, other complementary studies in blood cells seemed to be reasonable. In this research, we try to explore differentially expressed genes in peripheral blood mononuclear cells (PBMCs) of PBC patients. Nine PBC patients and 9 healthy controls were recruited as Cohort 1 for a microarray study of screening. Total RNA of PBMCs from each individual was isolated and screened by oligonucleotide microarray (22 K). Then, differentially expressed genes were categorized into signaling pathways. Expression levels of three important genes, tyrosine kinase binding protein (TYROBP), C-C motif chemokine 5 (CCL5) and cathepsin L (CTSL) were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) in a second Cohort 2 (30 PBC patients and 20 healthy controls). Results show that sixty-five genes differentially expressed in PBC were identified, 20 of which were up-regulated and 45 of which were down-regulated. Twenty-seven signaling pathways were identified. TYROBP and CCL5 were proved to be down-regulated in PBC, and CTSL was proved to be up-regulated (p<0.05) in PBC, which were all consistent with the screening study. In conclusions, the analysis of gene expression in PBMCs of PBC and the comparison of gene profiles between PBMCs and the liver may provide new clues to the pathogenesis of the disease.