Autocrine VEGF-VEGF-R loop on podocytes during glomerulonephritis in humans
Autocrine VEGF-VEGF-R loop on podocytes during glomerulonephritis in humans
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DOI：
10.1093/ndt/gfq200
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发表时间：
2010-10-01
影响因子：
6.1
通讯作者：
Hugo, Christian P. M.
中科院分区：
文献类型：
--
作者：
Hohenstein, Bernd;Colin, Maite;Hugo, Christian P. M.
方法：研究方法。本研究调查了153例肾小球肾炎(GN)患者的肾活检组织，并结合肾功能、损伤和修复指标，对肾小球血管内皮生长因子系统[血管内皮生长因子、血管内皮生长因子-R1、血管内皮生长因子-R2和由血管内皮生长因子受体复合体(VEGF-VEGF-R)鉴定的生物活性血管内皮生长因子]的表达和活性进行了研究。肾小球血管内皮生长因子表达明显升高，而血管内皮生长因子受体表达水平基本不变。在整体表达血管内皮生长因子的同时，血管内皮生长因子在其受体上的生物学活性显著增强。有趣的是，在肾小球肾炎过程中，血管内皮生长因子-R1和血管内皮生长因子-R2的表达模式发生了显著变化，出现了非常明显的足细胞模式，受体结合的血管内皮生长因子也被检测到。血管内皮生长因子的表达和活性可分别与肾小球增殖和肌酐等肾损伤指标相关联。本研究首次发现人肾小球肾炎过程中足细胞的血管内皮生长因子-血管内皮生长因子受体结合增加，提示不仅存在肾小球旁分泌促血管生成，而且血管内皮生长因子-受体系统在病变足细胞中具有自分泌作用。
Methods. The present study investigated a large number (n = 153) of renal biopsies from patients with glomerulonephritis (GN) and evaluated the expression and activity of the glomerular VEGF system [VEGF, VEGF-R1, VEGF-R2 and biologically active VEGF as identified by VEGF-VEGF receptor complexes (VEGF-VEGF-R)] in parallel with markers of renal function, injury and repair.Results. Whereas glomerular VEGF expression was clearly elevated, VEGF-R expression levels were widely unchanged. In parallel to the overall VEGF expression, the biological activity of VEGF on its receptors was uniformly significantly enhanced. Interestingly, the expression pattern of VEGF-R1 and VEGF-R2 significantly changed during GN where a very prominent podocytic pattern appeared, which was also detected for receptor-bound VEGF. VEGF expression and activity could be linked with indicators of renal injury such as glomerular proliferation and creatinine, respectively.Conclusions. This study shows, for the first time, increased podocytic VEGF-VEGF-R binding during human GN, suggesting not only the existence of a glomerular paracrine proangiogenic, but also an autocrine role of the VEGF-VEGF-R system in diseased podocytes.