葡萄糖6磷酸异构酶(G6PI)在细胞内是糖酵解关键酶，在细胞外又称为自分泌蠕动因子(AMF)，能促进肿瘤生长、转移和血管新生，也能诱导鼠发生关节炎。课题组研究发现类风湿关节炎（RA）患者外周血及关节液中G6PI含量异常增高、增高水平与病情活动正相关，并且G6PI能抑制关节滑膜成纤维样细胞(FLSs)凋亡。目前G6PI在RA发病机制中的作用尚未明。本项目继续深入，构建G6PI表达和siRNA干扰载体，从干扰FLSs细胞内G6PI表达和采用G6PI抑制剂、G6PI抗体、AMF受体（AMFR）抗体、AMFR-Fc融合蛋白干扰G6PI/AMFR信号通路两方面，研究G6PI调控RA-FLS增殖、凋亡、分泌炎症因子和促血管生成因子的作用，并采用体外、体内血管形成实验和G6PI诱导的RA模型来探明G6PI促滑膜血管新生作用，以初步阐明G6PI在RA关节滑膜增生、血管翳形成中的作用及分子机制。

Glucose-6 - phosphate isomerase (G6PI) is a ubiquitous cytosolic enzyme that catalyzes the second step in glycolysis. Molecular cloning and sequencing have identified G6PI as autocrine motility factor (AMF), also known as neuroleukin (NLK). AMF is a multifunctional cytokine that exhibits multifunctional growth factor-like activity via a unique cognate 78 kDa (gp78) seven-transmembrane glycoprotein receptor (autocrine motility factor receptor, AMFR). Overexpression of AMF and AMFR has been found in a wide spectrum of malignancies and is associated with cancer progression, metastasis, and angiogenesis. It has been reported that G6PI had the capacity to induce the chronic arthritis in mice. Our previous study found that the concentrations of soluble G6PI in the sera and synovial fluids of RA patients were elevated, and the sera GPI level correlated positively with the disease activity of RA. G6PI also enhanced the proliferation capacity and prohibit apoptosis on cultured RA-FLS. But so far it is remains unclear that pathogenic role. This study will continue to explore the following research on the basis of preliminary work: 1. To clarify the characteristic of G6PI /AMFR expression and autocrine G6PI on RA-FLS. 2. Construction the vectors of G6PI expression and siRNA interference, to investigate the changes of FLS on proliferation capacity and secretion of inflammatory cytokines after the G6PI expression is interference. 3. To explore the roles and its molecular mechanism of G6PI/AMFR pathway on FLS proliferation capacity and synovial angiogenesis by means of G6PI inhibitor, G6PI, anti-G6PI antibodies, anti-AMFR antibodies and AMFR-Fc fusion protein. 4. Using a variety of ways, including in vitro angiogenesis assay, in vivo matrigel plug assay and the mouse RA model, to verification the role of G6PI /AMFR pathway in induced synovial hyperplasia and angiogenesis.