Altered expression of microRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis
Altered expression of microRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis
复制标题
DOI：
10.1002/art.23386
复制
发表时间：
2008-04-01
影响因子：
--
通讯作者：
Kyburz, Diego
中科院分区：
文献类型：
--
作者：
Stanczyk, Joanna;Pedrioli, Deena A. Leslie;Kyburz, Diego
客观的。 MicroRNA (miRNA) 最近作为一类新的基因表达调节剂出现。在本研究中，我们研究了 miR-155 和 miR-146a 在类风湿性关节炎 (RA) 滑膜成纤维细胞 (RASF) 和 RA 滑膜组织中的表达、调控和功能。使用锁核酸微阵列来筛选经肿瘤坏死因子α（TNFα）处理的RASF中差异表达的miRNA。应用基于TaqMan的实时聚合酶链反应来测量miR-155和miR-146a的水平。强制过度表达 miR-155 用于研究 RASF 中 miR-155 的功能。结果。对用 TNF α 处理的 RASF 中表达的 miRNA 进行微阵列分析，结果显示 miR-155 显着上调。 RASF 中 miR-155 和 miR-146a 的组成型表达均高于骨关节炎 (OA) 患者，并且 TNF α、白细胞介素 1 β、脂多糖、聚 (I-C) 和细菌脂蛋白可进一步诱导 miR-155 的表达。 RA滑膜组织中miR-155的表达高于OA滑膜组织。研究发现 RASF 中 miR-155 的强制表达可抑制基质金属蛋白酶 3 (MMP-3) 的水平，并减少 Toll 样受体配体和细胞因子对 MMP 3 和 1 的诱导。此外，与来自RA外周血的单核细胞相比，RA滑液单核细胞表现出更高水平的miR-155。结论。这项研究首次描述了 RA 中 miRNA miR-155 和 miR-146a 表达增加。基于这些发现，我们推测炎症环境可能会改变类风湿关节常驻细胞中的 miRNA 表达谱。考虑到 miR-155 对 RASF 中 MMP 3 和 I 表达的抑制作用，我们假设 miR-155 可能参与调节 RASF 的破坏性。
Objective. MicroRNAs (miRNA) have recently emerged as a new class of modulators of gene expression. In this study we investigated the expression, regulation, and function of miR-155 and miR-146a in rheumatoid arthritis (RA) synovial fibroblasts (RASFs) and RA synovial tissue.Methods. Locked nucleic acid microarray was used to screen for differentially expressed miRNA in RASFs treated with tumor necrosis factor alpha (TNF alpha). TaqMan-based real-time polymerase chain reaction was applied to measure the levels of miR-155 and miR-146a. Enforced overexpression of miR-155 was used to investigate the function of miR-155 in RASFs.Results. Microarray analysis of miRNA expressed in RASFs treated with TNF alpha revealed a prominent up-regulation of miR-155. Constitutive expression of both miR-155 and miR-146a was higher in RASFs than in those from patients with osteoarthritis (OA), and expression of miR-155 could be further induced by TNF alpha, interleukin-1 beta, lipopolysaccharide, poly(I-C), and bacterial lipoprotein. The expression of miR-155 in RA synovial tissue was higher than in OA synovial tissue. Enforced expression of miR-155 in RASFs was found to repress the levels of matrix metalloproteinase 3 (MMP-3) and reduce the induction of MMPs 3 and 1 by Toll-like receptor ligands and cytokines. Moreover, compared with monocytes from RA peripheral blood, RA synovial fluid monocytes displayed higher levels of miR-155.Conclusion. This study provides the first description of increased expression of miRNA miR-155 and miR-146a in RA. Based on these findings, we postulate that the inflammatory milieu may alter miRNA expression profiles in resident cells of the rheumatoid joints. Considering the repressive effect of miR-155 on the expression of MMPs 3 and I in RASFs, we hypothesize that miR-155 may be involved in modulation of the destructive properties of RASFs.