Adiponectin isoforms: a potential therapeutic target in rheumatoid arthritis?
Adiponectin isoforms: a potential therapeutic target in rheumatoid arthritis?
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DOI：
10.1136/annrheumdis-2011-200924
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发表时间：
2012-10-01
影响因子：
27.4
通讯作者：
Neumann, Elena
中科院分区：
文献类型：
--
作者：
Frommer, Klaus W.;Schaeffler, Andreas;Neumann, Elena
目的脂联素参与类风湿关节炎（RA）的发病过程。从这个角度来看，脂联素可能是一个新的治疗靶点。然而，由于脂联素也在人类生物体中发挥有益作用，因此在保持积极作用的同时消除其有害作用的策略将是非常有利的。为了阐明这样一个战略，作者分析了不同的脂联素亚型是否会引起分歧的影响，特别是关于类风湿关节炎滑膜成纤维细胞（RASF），中央细胞类型的RA发病机制能够侵入和破坏cartilage.Methods Affyellow微阵列筛选RASF基因表达的变化。信使RNA水平通过实时PCR定量，蛋白质水平通过免疫测定定量。RASF和原代人淋巴细胞的迁移进行了分析，使用一个双室migration assay.Results在RASF中，个别脂联素亚型诱导RA发病机制相关的基因/蛋白，以明确不同程度。一般而言，最有效的同种型是高分子量/中分子量同种型和球形同种型，而最无效的同种型是脂联素三聚体。由RASF分泌的趋化因子脂联素刺激后，导致RASF和lymphocyte.Conclusion的迁移增加的结果清楚地表明，所有脂联素亚型在RA的病理生理的促炎性和联合破坏性的作用，表明在慢性炎症性关节疾病的不利影响超过脂联素的有益影响。
Objectives Several clinical studies have suggested the adipocytokine adiponectin is involved in the progression of rheumatoid arthritis (RA). From this point of view, adiponectin might present a new therapeutic target. However, as adiponectin also exerts beneficial effects in the human organism, a strategy that would allow its detrimental effects to be abolished while maintaining the positive effects would be highly favourable. To elucidate such a strategy, the authors analysed whether the different adiponectin isoforms induce diverging effects, especially with regard to rheumatoid arthritis synovial fibroblasts (RASF), a central cell type in RA pathogenesis capable of invading into and destroying cartilage.Methods Affymetrix microarrays were used to screen for changes in gene expression of RASF. Messenger RNA levels were quantified by real-time PCR, protein levels by immunoassay. The migration of RASF and primary human lymphocytes was analysed using a two-chamber migration assay.Results In RASF, the individual adiponectin isoforms induced numerous genes/proteins relevant in RA pathogenesis to clearly different extents. In general, the most potent isoforms were the high molecular weight/middle molecular weight isoforms and the globular isoform, while the least potent isoform was the adiponectin trimer. The chemokines secreted by RASF upon adiponectin stimulation resulted in an increased migration of RASF and lymphocytes.Conclusion The results clearly suggest a pro-inflammatory and joint-destructive role of all adiponectin isoforms in RA pathophysiology, indicating that in chronic inflammatory joint diseases the detrimental effects outweigh the beneficial effects of adiponectin.