Glucose-6-Phosphate Isomerase (G6PI) Mediates Hypoxia-Induced Angiogenesis in Rheumatoid Arthritis.
Glucose-6-Phosphate Isomerase (G6PI) Mediates Hypoxia-Induced Angiogenesis in Rheumatoid Arthritis.
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6-磷酸葡萄糖异构酶 (G6PI) 介导类风湿关节炎中缺氧诱导的血管生成
DOI：
10.1038/srep40274
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发表时间：
2017-01-09
影响因子：
4.6
通讯作者：
Fan LY
中科院分区：
文献类型：
--
作者：
Lu Y;Yu SS;Zong M;Fan SS;Lu TB;Gong RH;Sun LS;Fan LY
葡萄糖-6-磷酸异构酶（G6 PI）在类风湿关节炎（RA）患者的滑膜组织和滑液中均有较高水平的表达，但G6 PI在RA中的作用尚不清楚。在此，我们发现，在RA患者的滑膜组织的微血管内皮细胞中，G6 PI的富集，其中3%O2缺氧环境已被确定。为了确定RA中高G6 PI水平与低氧浓度之间的相关性，应用体外缺氧条件（~ 3%O2）来模拟体内RA环境。缺氧可促进类风湿关节炎滑膜成纤维细胞（RASFs）增殖，诱导人真皮微血管内皮细胞（HDMECs）迁移和血管生成管形成，并伴有G6 PI和HIF-1α表达增加。通过应用G6 PI功能丧失试验，我们证实了RA缺氧诱导表型需要G6 PI表达。此外，我们首次证明G6 PI在调节RASFs分泌VEGF以调节缺氧诱导的RA血管生成中起关键作用。总之，我们证明了一种新的途径调节缺氧诱导的血管生成RA介导的G6 PI。
The higher level of Glucose-6-phosphate isomerase (G6PI) has been found in both synovial tissue and synovial fluid of rheumatoid arthritis (RA) patients, while the function of G6PI in RA remains unclear. Herein we found the enrichment of G6PI in microvascular endothelial cells of synovial tissue in RA patients, where a 3% O2 hypoxia environment has been identified. In order to determine the correlation between the high G6PI level and the low oxygen concentration in RA, a hypoxia condition (~3% O2) in vitro was applied to mimic the RA environment in vivo. Hypoxia promoted cellular proliferation of rheumatoid arthritis synovial fibroblasts (RASFs), and induced cell migration and angiogenic tube formation of human dermal microvascular endothelial cells (HDMECs), which were accompanied with the increased expression of G6PI and HIF-1α. Through application of G6PI loss-of-function assays, we confirmed the requirement of G6PI expression for those hypoxia-induced phenotype in RA. In addition, we demonstrated for the first time that G6PI plays key roles in regulating VEGF secretion from RASFs to regulate the hypoxia-induced angiogenesis in RA. Taken together, we demonstrated a novel pathway regulating hypoxia-induced angiogenesis in RA mediated by G6PI.
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影响因子：
4.9
作者：
Akhavani MA;Madden L;Buysschaert I;Sivakumar B;Kang N;Paleolog EM
通讯作者：
Paleolog EM
岩藻糖基转移酶1介导类风湿关节炎中的血管生成。
影响因子：
13.3
作者：
Isozaki, Takeo;Amin, Mohammad A.;Ruth, Jeffrey H.;Campbell, Phillip L.;Tsou, Pei-Suen;Ha, Christine M.;Stinson, W. Alex;Domino, Steven E.;Koch, Alisa E.
通讯作者：
Koch, Alisa E.
影响因子：
4.9
作者：
Giatromanolaki, A;Sivridis, E;Koukourakis, MI
通讯作者：
Koukourakis, MI
影响因子：
11.2
作者：
Kho DH;Nangia-Makker P;Balan V;Hogan V;Tait L;Wang Y;Raz A
通讯作者：
Raz A
影响因子：
11.2
作者：
Kho DH;Zhang T;Balan V;Wang Y;Ha SW;Xie Y;Raz A
通讯作者：
Raz A