MicroRNAs in Rheumatoid Arthritis Potential Role in Diagnosis and Therapy
MicroRNAs in Rheumatoid Arthritis Potential Role in Diagnosis and Therapy
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DOI：
10.2165/11631480-000000000-00000
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发表时间：
2012-01-01
期刊：
影响因子：
6.8
通讯作者：
Gay, Steffen
中科院分区：
文献类型：
--
作者：
Filkova, Maria;Juengel, Astrid;Gay, Steffen
类风湿性关节炎（RA）是一种全身性、炎症性、自身免疫性疾病，伴有进行性关节损伤，可导致终身残疾。虽然在理解这种疾病方面取得了重大进展，但RA的发病机制尚未完全阐明。早期治疗可以预防严重残疾，并导致显着的患者的好处，虽然在相当数量的患者缺乏治疗效率仍然是一个问题。微小RNA（miRNA）是小的，非编码RNA，这取决于碱基配对的信使RNA（mRNA），介导mRNA切割，翻译抑制或mRNA不稳定。作为基因表达的微调调节因子，miRNA参与重要的细胞过程，并且它们的失调已经在不同疾病的许多细胞类型中被描述。在体液中，miRNA存在于微囊泡中或与Argonaute 2（Ago2）或高密度脂蛋白结合成复合物，并显示出高稳定性。因此，它们在日常诊断应用中作为疾病的潜在生物标志物是令人感兴趣的。通过获得或丧失功能的方法靶向miRNA已经在各种动物模型中产生了治疗效果。在过去的几年中，已经清楚地发现RA患者中存在miRNA表达的改变。越来越多的研究表明，外周血单核细胞或分离的T淋巴细胞、滑膜组织和滑膜成纤维细胞（被认为是关节破坏中的关键效应细胞）中的miRNA的失调有助于炎症、细胞外基质的降解和驻留细胞的侵袭行为。因此，miRNAs维持典型的RA的病理生理过程。目前的审查的目的是讨论现有的证据连接的miRNAs的表达，炎症和免疫反应在RA和其潜在的生物标志物和治疗RA患者的新目标。
Rheumatoid arthritis (RA) is a systemic, inflammatory, autoimmune disorder with progressive articular damage that may result in lifelong disability. Although major strides in understanding the disease have been made, the pathogenesis of RA has not yet been fully elucidated. Early treatment can prevent severe disability and lead to remarkable patient benefits, although a lack of therapeutic efficiency in a considerable number of patients remains problematic.MicroRNAs (miRNAs) are small, non-coding RNAs that, depending upon base pairing to messenger RNA (mRNA), mediate mRNA cleavage, translational repression or m RNA destabilization. As fine tuning regulators of gene expression, miRNAs are involved in crucial cellular processes and their dysregulation has been described in many cell types in different diseases. In body fluids, miRNAs are present in microvesicles or incorporated into complexes with Argonaute 2 (Ago2) or high-density lipoproteins and show high stability. Therefore, they are of interest as potential biomarkers of disease in daily diagnostic applications. Targeting miRNAs by gain or loss of function approaches have brought therapeutic effects in various animal models.Over the past several years it has become clear that alterations exist in the expression of miRNAs in patients with RA. Increasing numbers of studies have shown that dysregulation of miRNAs in peripheral blood mononuclear cells or isolated T lymphocytes, in synovial tissue and synovial fibroblasts that are considered key effector cells in joint destruction, contributes to inflammation, degradation of extracellular matrix and invasive behaviour of resident cells. Thereby, miRNAs maintain the pathophysiological process typical of RA.The aim of the current review is to discuss the available evidence linking the expression of miRNAs to inflammatory and immune response in RA and their potential as biomarkers and the novel targets for treatment in patients with RA.