Center of Experimental Rheumatology, University Hospital Zürich, Zürich, Switzerland.
BioDrugs. 2012 Jun 1;26(3):131-41. doi: 10.2165/11631480-000000000-00000.
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 mRNA 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.
类风湿关节炎(RA)是一种系统性、炎症性、自身免疫性疾病,具有进行性关节损伤,可能导致终身残疾。尽管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,并给患者带来显著的益处,尽管相当一部分患者的治疗效果仍然存在问题。微 RNA(miRNA)是一种小的非编码 RNA,根据与信使 RNA(mRNA)的碱基配对,可以介导 mRNA 切割、翻译抑制或 mRNA 不稳定。作为基因表达的精细调节因子,miRNA 参与了关键的细胞过程,其在许多不同疾病的细胞类型中的失调已经被描述。在体液中,miRNA 存在于微泡中或与 Argonaute 2(Ago2)或高密度脂蛋白结合形成复合物,并显示出高度的稳定性。因此,它们作为疾病的潜在生物标志物在日常诊断应用中具有吸引力。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带来了治疗效果。在过去的几年中,已经清楚地表明,RA 患者的 miRNA 表达存在改变。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中 miRNA 的失调,这些细胞被认为是关节破坏的关键效应细胞,导致炎症、细胞外基质降解和驻留细胞的侵袭行为。因此,miRNA 维持了 RA 典型的病理生理过程。本综述的目的是讨论将 miRNA 的表达与 RA 中的炎症和免疫反应联系起来的现有证据,以及它们作为生物标志物和 RA 患者治疗新靶点的潜力。
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