Local VEGF activity but not VEGF expression is tightly regulated during diabetic nephropathy in man
Local VEGF activity but not VEGF expression is tightly regulated during diabetic nephropathy in man
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DOI：
10.1038/sj.ki.5000294
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发表时间：
2006-05-01
影响因子：
19.6
通讯作者：
Hugo, CPM
中科院分区：
文献类型：
--
作者：
Hohenstein, B;Hausknecht, B;Hugo, CPM
一些研究表明血管生成细胞因子血管内皮生长因子（VEGF）与糖尿病肾病的发展有关，但没有关于其在人类疾病中的局部活性的数据。对52例II型糖尿病患者的肾小球活检进行评估，并与10例无肾脏疾病的肾活检（对照组）进行比较。研究了肾小球硬化、毛细血管稀疏、肾小球和内皮细胞增殖、凋亡、VEGF表达以及指示局部VEGF活性的受体结合VEGF，以及信号转导分子Akt的磷酸化。由于单个活检中肾小球病变的异质性，这些参数与单个肾小球的损伤程度相关，而不是与活检相关。严重的肾小球毛细血管稀疏与肾小球硬化程度有关。虽然检测到细胞凋亡与损伤阶段无关，但内皮细胞增殖表明毛细血管修复仅在轻度/中度损伤的肾小球中显着增加。在对照组中，VEGF主要在足细胞中表达，而受体结合的VEGF仅限于肾小球内皮。VEGF表达在所有糖尿病肾小球中通过许多不同的细胞类型增加。相比之下，VEGF受体激活在轻度损伤的肾小球内皮中主要增加，而在较严重损伤的肾小球内皮中显著降低。糖尿病肾病与肾小球毛细血管稀疏有关。尽管肾小球VEGF总体增加，内皮上受体结合的VEGF减少可能是毛细血管修复反应不足的一个指标。
Several studies have implicated the angiogenic cytokine vascular endothelial growth factor ( VEGF) in the development of diabetic nephropathy, but no data are available about its local activity during human disease. Glomeruli from 52 archival biopsies from type II diabetics were evaluated and compared to 10 renal biopsies without kidney disease ( controls). Glomerulosclerosis, capillary rarefaction, glomerular and endothelial cell proliferation, apoptosis, VEGF expression, as well as receptor-bound VEGF indicating local VEGF activity, and phosphorylation of the signal transduction molecule Akt were investigated. Owing to substantial heterogeneity of glomerular lesions in individual biopsies, these parameters were correlated with the degree of injury in individual glomeruli rather than biopsies. Severe glomerular capillary rarefaction was linked to the degree of glomerulosclerosis. While cellular apoptosis was detected independent of the stage of injury, endothelial cell proliferation indicating capillary repair was markedly increased only in mildly/moderately injured glomeruli. In controls, VEGF was predominantly expressed in podocytes, whereas receptor-bound VEGF was confined to the glomerular endothelium. VEGF expression was increased in all diabetic glomeruli by many different cell types. In contrast, VEGF receptor activation was increased predominantly in the endothelium of only mildly injured glomeruli, but significantly decreased in more severely injured glomeruli. Diabetic nephropathy is associated with glomerular capillary rarefaction. Despite overall increased glomerular VEGF, the decreased receptor-bound VEGF on the endothelium may be an indicator of an insufficient capillary repair reaction.