Enhanced expression of ANGPTL2 in the microvascular lesions of diabetic glomerulopathy

Enhanced expression of ANGPTL2 in the microvascular lesions of diabetic glomerulopathy
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DOI:
10.1159/000100493
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发表时间:
2007-01-01
影响因子:
--
通讯作者:
Li, Lei-shi
Li, Lei-shi
中科院分区:
其他
文献类型:
--
作者:
Sun, Hua;Zheng, Jing-min;Li, Lei-shi

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【摘要】:背景:糖尿病肾病(DN)是糖尿病最重要的微血管并发症之一。然而,其根本机制仍不清楚。我们研究了血管生成素样 2 (ANGPTL2) 的表达特征,这是我们之前的基因芯片筛选中发现的一种新型 DN 相关生长因子。方法:从 24 名 DN 患者和 8 名供体对照的肾活检中显微解剖肾小球。通过RT-PCR和免疫组化检测ANGPTL2的表达,然后与肾小球损伤的临床和病理指标相关。结果:与基因芯片实验的结果一致,与供体对照相比,ANGPTL2 在糖尿病肾小球中更频繁地表达(95% vs. 38%,chi(2) = 15.9,p < 0.01)。 ANGPTL2 mRNA 上调在微动脉瘤(22% vs. 66%,p < 0.05)、炎症流入(6 vs. 50%,p < 0.05)或内皮泡沫细胞形成(11 vs. 53%,p < 0.05)较少的肾小球中更为显着。免疫染色显示肥大的糖尿病肾小球中ANGPTL2蛋白表达上调,主要分布在足细胞中,这被认为是ANGPTL2的起源。结论:糖尿病肾小球病中ANGPTL2的上调与微血管异常和内皮炎症密切相关。 ANGPTL2可能在糖尿病肾小球病的发病机制中发挥重要作用。版权所有 (c) 2007 S. Karger AG,巴塞尔。
Background: Diabetic nephropathy (DN) is one of the most important microvascular complications of diabetes mellitus. However, the underlying mechanisms remain unclear. We studied the expression characteristics of angiopoietin-like 2 (ANGPTL2), a novel DN-associated growth factor identified in our previous gene chip screening. Methods: Glomeruli were microdissected from renal biopsies from 24 patients with DN and 8 donor controls. The expression of ANGPTL2 was assessed by RT-PCR and immunohistochemistry, and then correlated with clinical and pathological indices of glomerular injury. Results: Consistent with the results of the gene chip experiment, abundant expression of ANGPTL2 was found more frequently in diabetic glomeruli as compared to donor controls (95 vs. 38%, chi(2) = 15.9, p < 0.01). ANGPTL2 mRNA upregulation was more prominent in glomeruli with less microaneurysm (22 vs. 66%, p < 0.05), inflammatory influx (6 vs. 50%, p < 0.05) or endothelial foam cell formation (11 vs. 53%, p < 0.05). Immunostaining revealed an upregulation of ANGPTL2 protein in hypertrophied diabetic glomeruli, mainly distributed in podocytes, which were supposed to be the origin of ANGPTL2. Conclusion: The upregulation of ANGPTL2 in diabetic glomerulopathy shows a close relationship to abnormal microvasculature and endothelial inflammation. ANGPTL2 may play an important role in the pathogenesis of diabetic glomerulopathy. Copyright (c) 2007 S. Karger AG, Basel.