Hypoxia-Inducible Factor (HIF) as a Target for Novel Therapies in Rheumatoid Arthritis.
Hypoxia-Inducible Factor (HIF) as a Target for Novel Therapies in Rheumatoid Arthritis.
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DOI：
10.3389/fphar.2016.00184
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发表时间：
2016
影响因子：
5.6
通讯作者：
Dias TH
中科院分区：
文献类型：
--
作者：
Hua S;Dias TH
缺氧是类风湿关节炎（RA）的重要微环境特征。低氧诱导因子（HIF）是RA滑膜中高表达的关键转录因子，调节RA对低氧环境的适应性反应。越来越多的证据支持缺氧和HIF调节RA的许多重要病理生理学特征，包括滑膜炎症、血管生成和软骨破坏。实验和临床数据均证实RA中HIF-1α和HIF-2α均上调。本文将重点介绍滑膜关节内HIF的差异表达及其在不同细胞类型中调节RA进展的功能行为。还将讨论针对RA疾病部位的HIF调节途径的新治疗策略的潜在开发。
Hypoxia is an important micro-environmental characteristic of rheumatoid arthritis (RA). Hypoxia-inducible factors (HIF) are key transcriptional factors that are highly expressed in RA synovium to regulate the adaptive responses to this hypoxic milieu. Accumulating evidence supports hypoxia and HIFs in regulating a number of important pathophysiological characteristics of RA, including synovial inflammation, angiogenesis, and cartilage destruction. Experimental and clinical data have confirmed the upregulation of both HIF-1α and HIF-2α in RA. This review will focus on the differential expression of HIFs within the synovial joint and its functional behavior in different cell types to regulate RA progression. Potential development of new therapeutic strategies targeting HIF-regulated pathways at sites of disease in RA will also be addressed.