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缺氧诱导因子-1(HIF-1)是一种由缺氧诱导细胞产生的调节细胞氧平衡和缺氧反应基因表达的核转录因子。缺氧条件下,细胞核产生HIF-1与靶基因结合,促进靶基因转录,引起一系列细胞对缺氧的反应,在促进糖酵解、促进血管生成、红细胞生成及调节血管舒缩等方面具有重要的作用。在类风湿关节炎(RA)中,HIF-1的表达增加可能通过上调血管内皮生长因子及其受体表达调控糖酵解代谢,从而启动并持续炎症反应,上调转录因子Ets-1的表达,激活CXCL12/CXCR4通路,与诱导型一氧化氮合酶相互作用及影响细胞凋亡等机制参与RA的发病。HIF-1为RA的基因治疗提供了新途径。
Hypoxia-inducible factor-1 (HIF-1) is a nuclear transcription factor that regulates cellular oxygen balance and hypoxia-responsive gene expression produced by hypoxia-inducible cells. Hypoxia, the nucleus produce HIF-1 and target genes to promote transcription of the target gene, causing a series of cell response to hypoxia, in promoting glycolysis, promote angiogenesis, erythropoiesis and regulation of vasomotor and so on have Important role. In rheumatoid arthritis (RA), the increased expression of HIF-1 may regulate the glycolytic metabolism by up-regulating the expression of vascular endothelial growth factor and its receptor, thereby initiating and continuing the inflammatory response, upregulating the expression of the transcription factor Ets-1, Activation of CXCL12 / CXCR4 pathway, interaction with inducible nitric oxide synthase and the mechanism of affecting apoptosis participate in the pathogenesis of RA. HIF-1 provides a new way for the gene therapy of RA.