Zhang Lei, Ma Danxu, Li Xi, Deng Chuiwen, Shi Qun, You Xin, Leng Xiaomei, Li Mengtao, Tang Fulin, Zhang Fengchun, Li Yongzhe
Clin Exp Med. 2014 Nov;14(4):409-16. doi: 10.1007/s10238-013-0253-6.
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.
先前关于原发性胆汁性肝硬化（PBC）基因表达谱的研究仅聚焦于肝组织或肝内细胞。由于该病理过程是全身性的，因此对血细胞进行其他补充研究似乎是合理的。在本研究中，我们试图探索PBC患者外周血单个核细胞（PBMC）中差异表达的基因。招募了9例PBC患者和9名健康对照作为队列1进行筛选的微阵列研究。分离每个个体PBMC的总RNA，并通过寡核苷酸微阵列（22K）进行筛选。然后，将差异表达的基因归类到信号通路中。在第二个队列2（30例PBC患者和20名健康对照）中，通过定量实时聚合酶链反应（qRT-PCR）确认了三个重要基因酪氨酸激酶结合蛋白（TYROBP）、C-C基序趋化因子5（CCL5）和组织蛋白酶L（CTSL）的表达水平。结果显示，共鉴定出65个在PBC中差异表达的基因，其中20个上调，45个下调。鉴定出27条信号通路。证实TYROBP和CCL5在PBC中下调，CTSL在PBC中上调（p<0.05），这些均与筛选研究结果一致。总之，对PBC患者PBMC中的基因表达进行分析以及比较PBMC与肝脏之间的基因谱，可能为该疾病的发病机制提供新线索。
