miRNA可成为干燥综合征唾液腺炎症及功能减退的标志物
发表者：张警丰
日期：2015-03-04
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摘要（美国国家卫生研究院） 目的：miRNAs可反映生理及病理过程，因此可作为一些复杂情况如自身免疫性疾病病理生理过程的标志物。我们将SS患者分为低炎症活动度，唾液分泌正常组及高炎症活动度，唾液分泌受损者，并以非SS患者作为对照，取唾液腺做miRNA微阵列芯片分析，以判断唾液腺炎症及功能损伤时miRNA表达类型。
方法：miRNA表达谱应用Agilent miRNA微阵列芯片分析。我们采用了新的方法进行数据标准化，即定义看家miRNA。应用自动数学分析方法比较不同组别的SS与对照组间miRNA表达的不同。应用生物信息学方法预测不同表达的miRNA所靶向的信使RNA。
结果：高炎症活动度SS、低炎症活动度SS及正常对照间唾液腺miRNA表达类型截然不同。应用实时定量PCR方法我们证实了2种miRNA作为SS炎症的独立标志物。低唾液流率者较高唾液流率者miRNA表达谱不同，在唾液腺功能减低者中大部分相关miRNA表达上调，提示相应miRNA靶点具有上皮细胞保护作用。我们所预测的炎症及唾液腺功能减低的相关miRNA生物靶点具有重叠性并具有各自不同的生物学途径及调控过程。
结论：SS患者唾液腺炎症及功能减退具有特异的miRNA表达谱，相应miRNA可能成为新的生物标志物。
附原文：Abstract：OBJECTIVE:MicroRNA reflect physiologic and pathologic processes and may be used as biomarkers of concurrent pathophysiologic events in complex settings such as autoimmune diseases. We generated microRNA microarray profiles from the minor salivary glands of control subjects without Sjögren's syndrome (SS) and patients with SS who had low-grade or high-grade inflammation and impaired or normal saliva production, to identify microRNA patterns specific to salivary gland inflammation or dysfunction.METHODS:MicroRNA expression profiles were generated by Agilent microRNA arrays. We developed a novel method for data normalization by identifying housekeeping microRNA.MicroRNA profiles were compared by unsupervised mathematical methods to test how well they distinguish between control subjects and various subsets of patients with SS. Several bioinformatics methods were used to predict the messenger RNA targets of the differentially expressed microRNA.RESULTS:MicroRNA expression patterns accurately distinguished salivary glands from control subjects and patients with SS who had low-degree or high-degree inflammation. Using real-time quantitative polymerase chain reaction, we validated 2 microRNA as markers of inflammation in an independent cohort. Comparing microRNA from patients with preserved or low salivary flow identified a set of differentially expressed microRNA, most of which were up-regulated in the group with decreased salivary gland function, suggesting that the targets of microRNA may have a protective effect on epithelial cells. The predicted biologic targets of microRNA associated with inflammation or salivary gland dysfunction identified both overlapping and distinct biologic pathways and processes.CONCLUSION: Distinct microRNA expression patterns are associated with salivary gland inflammation and dysfunction in patients with SS, and microRNA represent a novel group of potential biomarkers.
引自：Alevizos I, Alexander S, Turner RJ, Illei GG. MicroRNA expression profiles as biomarkers of minor salivary gland inflammation and dysfunction in Sjögren's syndrome. Arthritis Rheum. 2011 Feb;63(2):535-44. （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）
方法：miRNA表达谱应用Agilent miRNA微阵列芯片分析。我们采用了新的方法进行数据标准化，即定义看家miRNA。应用自动数学分析方法比较不同组别的SS与对照组间miRNA表达的不同。应用生物信息学方法预测不同表达的miRNA所靶向的信使RNA。
结果：高炎症活动度SS、低炎症活动度SS及正常对照间唾液腺miRNA表达类型截然不同。应用实时定量PCR方法我们证实了2种miRNA作为SS炎症的独立标志物。低唾液流率者较高唾液流率者miRNA表达谱不同，在唾液腺功能减低者中大部分相关miRNA表达上调，提示相应miRNA靶点具有上皮细胞保护作用。我们所预测的炎症及唾液腺功能减低的相关miRNA生物靶点具有重叠性并具有各自不同的生物学途径及调控过程。
结论：SS患者唾液腺炎症及功能减退具有特异的miRNA表达谱，相应miRNA可能成为新的生物标志物。
附原文：Abstract：OBJECTIVE:MicroRNA reflect physiologic and pathologic processes and may be used as biomarkers of concurrent pathophysiologic events in complex settings such as autoimmune diseases. We generated microRNA microarray profiles from the minor salivary glands of control subjects without Sjögren's syndrome (SS) and patients with SS who had low-grade or high-grade inflammation and impaired or normal saliva production, to identify microRNA patterns specific to salivary gland inflammation or dysfunction.METHODS:MicroRNA expression profiles were generated by Agilent microRNA arrays. We developed a novel method for data normalization by identifying housekeeping microRNA.MicroRNA profiles were compared by unsupervised mathematical methods to test how well they distinguish between control subjects and various subsets of patients with SS. Several bioinformatics methods were used to predict the messenger RNA targets of the differentially expressed microRNA.RESULTS:MicroRNA expression patterns accurately distinguished salivary glands from control subjects and patients with SS who had low-degree or high-degree inflammation. Using real-time quantitative polymerase chain reaction, we validated 2 microRNA as markers of inflammation in an independent cohort. Comparing microRNA from patients with preserved or low salivary flow identified a set of differentially expressed microRNA, most of which were up-regulated in the group with decreased salivary gland function, suggesting that the targets of microRNA may have a protective effect on epithelial cells. The predicted biologic targets of microRNA associated with inflammation or salivary gland dysfunction identified both overlapping and distinct biologic pathways and processes.CONCLUSION: Distinct microRNA expression patterns are associated with salivary gland inflammation and dysfunction in patients with SS, and microRNA represent a novel group of potential biomarkers.
引自：Alevizos I, Alexander S, Turner RJ, Illei GG. MicroRNA expression profiles as biomarkers of minor salivary gland inflammation and dysfunction in Sjögren's syndrome. Arthritis Rheum. 2011 Feb;63(2):535-44. （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）