Expression of lysophosphatidic acid, autotaxin and acylglycerol kinase as biomarkers in diabetic retinopathy
Expression of lysophosphatidic acid, autotaxin and acylglycerol kinase as biomarkers in diabetic retinopathy
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DOI：
10.1007/s00592-012-0422-1
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发表时间：
2013-06-01
影响因子：
3.8
通讯作者：
Opdenakker, Ghislain
中科院分区：
文献类型：
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作者：
Abu El-Asrar, Ahmed M.;Mohammad, Ghulam;Opdenakker, Ghislain
促炎性溶血磷脂酸（LPA）是几种转录因子和信号通路的有效激活剂，并且是参与炎症、血管生成和纤维化的基因的有效调节剂。本研究旨在检测增生性糖尿病视网膜病变（PDR）患者玻璃体液中LPA和LPA产生酶、自分泌运动因子（ATX）和酰基甘油激酶（AGK）的水平，并将其水平与临床疾病活动度和血管内皮生长因子（VEGF）水平相关联。此外，我们还检测了ATX、AGK和VEGF受体-2（VEGFR-2）在糖尿病大鼠视网膜中的表达。采用酶联免疫吸附试验对42例PDR和35例非糖尿病患者的玻璃体样本进行了研究。通过Western印迹分析检测大鼠的玻璃体样品和视网膜。PDR患者玻璃体样本中的VEGF、LPA和AGK水平显著高于无糖尿病的对照患者（所有比较p < 0.001）。活动性新血管形成的PDR和非活动性PDR患者的ATX水平显著低于非糖尿病患者（p = 0.045）。有活跃新生血管的PDR患者的平均VEGF和AGK水平显著高于非活跃PDR和非糖尿病患者（两种比较均为p < 0.001）。PDR患者VEGF水平与AGK水平显著相关（r = 0.954; p < 0.001）。Western blot分析显示，与非糖尿病对照组相比，糖尿病大鼠玻璃体样本和视网膜中AGK和VEGFR-2的表达显著增加，而ATX显著下调。我们的研究结果表明，ATX-AGK-LPA信号轴可能是糖尿病视网膜病变的发生和发展的重要参与者。
The proinflammatory lysophosphatidic acid (LPA) is a potent activator of several transcriptional factors and signaling pathways and a potent modulator of genes involved in inflammation, angiogenesis and fibrosis. This study was conducted to measure the levels of LPA and LPA-producing enzymes, autotaxin (ATX) and acylglycerol kinase (AGK) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the level of vascular endothelial growth factor (VEGF). In addition, we examined the expression of ATX, AGK and VEGF receptor-2 (VEGFR-2) in the retinas of diabetic rats. Vitreous samples from 42 PDR and 35 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Vitreous samples and retinas of rats were examined by Western blot analysis. VEGF, LPA and AGK levels in vitreous samples from PDR patients were significantly higher than those in control patients without diabetes (p < 0.001 for all comparisons). ATX levels in PDR with active neovascularization and inactive PDR were significantly lower than those in nondiabetic patients (p = 0.045). Mean VEGF and AGK levels in PDR with active neovascularization were significantly higher than those in inactive PDR and nondiabetic patients (p < 0.001 for both comparisons). A significant correlation was observed between levels of VEGF and levels of AGK in PDR patients (r = 0.954; p < 0.001). Western blot analysis revealed a significant increase in the expression of AGK and VEGFR-2 in vitreous samples and the retinas of diabetic rats compared to nondiabetic controls, whereas ATX was significantly downregulated. Our findings suggest that ATX-AGK-LPA signaling axis might be an important player in the development and progression of diabetic retinopathy.