Patel Leena, Thaker Aswin
Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology , Anand, Gujarat , India and.
Ren Fail. 2014 Jul;36(6):916-24. doi: 10.3109/0886022X.2014.900404. Epub 2014 Mar 31.
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. The pathophysiologic mechanisms of diabetic nephropathy are incompletely understood but include overproduction of various growth factors and cytokines. Upregulation of vascular endothelial growth factor (VEGF) is a pathogenic event occurring in most forms of podocytopathy; however, the mechanisms that regulate this growth factor induction are not clearly identified. A2B receptors have been found to regulate VEGF expression under hypoxic environment in different tissues. One proposed hypothesis in mediating diabetic nephropathy is the modulation of VEGF-NO balance in renal tissue. We determined the role of adenosine A2B receptor in mediating VEGF overproduction and nitrite in diabetic nephropathy. The renal content of A2B receptors and VEGF was increased after 8 weeks of diabetes induction. The renal and plasma nitrite levels were also reduced in these animals. In vivo administration of A2B adenosine receptor antagonist (MRS1754) inhibited the renal over expression of VEGF and adverse renal function parameters. The antagonist administration also improved the kidney tissue nitrite levels. In conclusion, we demonstrated that VEGF induction via adenosine signaling might be the critical event in regulating VEGF-NO axis in diabetic nephropathy.
糖尿病肾病（DN）是全球终末期肾病最常见的病因。糖尿病肾病的病理生理机制尚未完全明确，但包括多种生长因子和细胞因子的过度产生。血管内皮生长因子（VEGF）的上调是大多数形式的足细胞病中发生的致病事件；然而，调节这种生长因子诱导的机制尚未明确。已发现A2B受体在不同组织的低氧环境下调节VEGF表达。介导糖尿病肾病的一个提出的假说是肾组织中VEGF-NO平衡的调节。我们确定了腺苷A2B受体在介导糖尿病肾病中VEGF过度产生和亚硝酸盐中的作用。诱导糖尿病8周后，肾脏A2B受体和VEGF的含量增加。这些动物的肾脏和血浆亚硝酸盐水平也降低。体内给予A2B腺苷受体拮抗剂（MRS1754）可抑制VEGF在肾脏的过度表达以及不良肾功能参数。拮抗剂给药还改善了肾脏组织亚硝酸盐水平。总之，我们证明通过腺苷信号传导诱导VEGF可能是调节糖尿病肾病中VEGF-NO轴的关键事件。
