Promoting effects of the adipokine, apelin, on diabetic nephropathy.

Promoting effects of the adipokine, apelin, on diabetic nephropathy.
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DOI:
10.1371/journal.pone.0060457
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zeng XJ
Zeng XJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang BH;Wang W;Wang H;Yin J;Zeng XJ

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血管生成、肾小球通透性增加和蛋白尿被认为是糖尿病肾病(DN)进展的原因。Apelin受体及其内源性配体Apelin以自分泌或旁分泌方式诱导内皮细胞出芽,可能是DN的发病机制之一。本研究旨在探讨Apelin在DN发病机制中的作用。因此,我们观察了2型糖尿病患者肾脏中apelin/APLNR的表达以及2型糖尿病患者白蛋白尿与血清apelin的相关性。我们还测量了apelin对肾小球内皮细胞的增殖、迁移和趋化作用。为了测量apelin在肾小球内皮细胞中的渗透性,我们使用transwells检测FITC-BSA通过单层肾小球内皮细胞的渗透。结果显示,与健康人相比,2型糖尿病患者的血清apelin显著更高(p<0.05,图1B),并且尿白蛋白与血清apelin正相关(R = 0.78,p<0.05)。  Apelin可剂量依赖性地促进肾小球内皮细胞的迁移、增殖和趋化(p<0.05)。Apelin还可促进肾小球内皮细胞通透性(p<0.05),上调肾小球内皮细胞VEGF 2和Tie 2的表达(p<0.05)。这些结果表明,在2型糖尿病中上调的爱帕琳蛋白(这可能归因于增加的脂肪量)促进肾小球中的血管生成以形成异常血管,并且增强的爱帕琳蛋白通过上调肾小球内皮细胞中VEGFR 2和Tie 2的表达来增加渗透性。
Angiogenesis, increased glomerular permeability, and albuminuria are thought to contribute to the progression of diabetic nephropathy (DN). Apelin receptor (APLNR) and the endogenous ligand of APLNR, apelin, induce the sprouting of endothelial cells in an autocrine or paracrine manner, which may be one of the mechanisms of DN. The aim of this study was to investigate the role of apelin in the pathogenesis of DN. Therefore, we observed apelin/APLNR expression in kidneys from patients with type 2 diabetes as well as the correlation between albuminuria and serum apelin in patients with type 2 diabetes. We also measured the proliferating, migrating, and chemotactic effects of apelin on glomerular endothelial cells. To measure the permeability of apelin in glomerular endothelial cells, we used transwells to detect FITC-BSA penetration through monolayered glomerular endothelial cells. The results showed that serum apelin was significantly higher in the patients with type 2 diabetes compared to healthy people (p<0.05, Fig. 1B) and that urinary albumin was positively correlated with serum apelin (R = 0.78, p<0.05). Apelin enhanced the migration, proliferation, and chemotaxis of glomerular endothelial cells in a dose-dependent manner (p<0.05). Apelin also promoted the permeability of glomerular endothelial cells (p<0.05) and upregulated the expression of VEGFR2 and Tie2 in glomerular endothelial cells (p<0.05). These results indicated that upregulated apelin in type 2 diabetes, which may be attributed to increased fat mass, promotes angiogenesis in glomeruli to form abnormal vessels and that enhanced apelin increases permeability via upregulating the expression of VEGFR2 and Tie2 in glomerular endothelial cells.
DOI: 10.1093/ndt/14.2.348
发表时间: 1999-02-01
影响因子: 6.1
作者:
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