Expression of MicroRNA-146 in rheumatoid arthritis synovial tissue
Expression of MicroRNA-146 in rheumatoid arthritis synovial tissue
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DOI：
10.1002/art.23429
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发表时间：
2008-05-01
影响因子：
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通讯作者：
Asahara, Hiroshi
中科院分区：
文献类型：
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作者：
Nakasa, Tomoyuki;Miyaki, Shigeru;Asahara, Hiroshi
Objective.与22个核苷酸的非编码RNA类似的几种microRNA表现出组织特异性或发育阶段特异性表达模式，并与人类疾病相关。本研究的目的是确定microRNA-146（miR-146）在类风湿关节炎（RA）患者滑膜组织中的表达模式。通过定量逆转录-聚合酶链反应（RT-PCR）、原位杂交和组织切片免疫组织化学分析了5例RA患者、5例骨关节炎（OA）患者和1例正常受试者滑膜组织中miR-146的表达。通过定量PCR和RT-PCR检测肿瘤坏死因子α（TNF α）和白细胞介素-1 β（IL-1 β）刺激培养的人类风湿关节炎滑膜成纤维细胞（RASFs）后miR-146的诱导。成熟miR-146 a和原代miR-146 a/B在RA滑膜组织中高表达，RA滑膜组织也表达TNF α，但这2种microRNA在OA和正常滑膜组织中表达较低。原位杂交结果显示，RA患者滑膜组织中，miR-146 a主要表达于表层和下层细胞。miR-146 a阳性细胞主要是CD 68+巨噬细胞，但包括几种CD 3 + T细胞亚群和CD 79 a + B细胞。TNF α和IL-1 β刺激RASFs后，miR-146 a/B的表达显著上调。这项研究表明，miR-146在RA滑膜组织中表达，并且其表达由TNF α和IL-1 β刺激诱导。需要进一步的研究来阐明miR-146在这些组织中的功能。
Objective. Several microRNA, which are similar to 22-nucleotide noncoding RNAs, exhibit tissue-specific or developmental stage-specific expression patterns and are associated with human diseases. The objective of this study was to identify the expression pattern of microRNA-146 (miR-146) in synovial tissue from patients with rheumatoid arthritis (RA).Methods. The expression of miR-146 in synovial tissue from 5 patients with RA, 5 patients with osteoarthritis (OA), and 1 normal subject was analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and by in situ hybridization and immunohistochemistry of tissue sections. Induction of miR-146 following stimulation with tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) of cultures of human rheumatoid arthritis synovial fibroblasts (RASFs) was examined by quantitative PCR and RT-PCR.Results. Mature miR-146a and primary miR146a/b were highly expressed in RA synovial tissue, which also expressed TNF alpha, but the 2 microRNA were less highly expressed in OA and normal synovial tissue. In situ hybridization showed primary miR-146a expression in cells of the superficial and sublining layers in synovial tissue from RA patients. Cells positive for miR-146a were primarily CD68+ macrophages, but included several CD3+ T cell subsets and CD79a+ B cells. Expression of miR-146a/b was markedly upregulated in RASFs after stimulation with TNF alpha and IL-1 beta.Conclusion. This study shows that miR-146 is expressed in RA synovial tissue and that its expression is induced by stimulation with TNF alpha and IL-1 beta. Further studies are required to elucidate the function of miR-146 in these tissues.