Glomerular endothelial cell injury and damage precedes that of podocytes in adriamycin-induced nephropathy.
Glomerular endothelial cell injury and damage precedes that of podocytes in adriamycin-induced nephropathy.
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DOI：
10.1371/journal.pone.0055027
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Sun YB;Qu X;Zhang X;Caruana G;Bertram JF;Li J
足细胞在肾小球疾病的发生和发展中的作用在过去的十年中得到了广泛的研究。然而，肾小球内皮细胞在蛋白尿和肾小球硬化症发病机制中的重要性在很大程度上被忽视。最近的研究表明，内皮型一氧化氮合酶（eNOS）缺乏加剧了抗GBM和残余肾模型中的肾损伤，并加速了糖尿病肾损伤。越来越多的证据也表明肾小球内皮细胞在预防蛋白尿中的重要性。我们假设内皮功能障碍可以启动和促进肾小球疾病的发展和进展。阿霉素（ADR）给药C57 BL/6小鼠，通常是一个ADR耐药株，与eNOS缺乏诱导明显的蛋白尿，严重的肾小球硬化，间质纤维化和炎症。我们还研究了肾小球内皮细胞和足细胞损伤的ADR诱导的肾病Balb/c小鼠，ADR敏感株，通过免疫染色，TUNEL和蛋白质印迹。有趣的是，eNOS的下调和凋亡的肾小球内皮细胞的外观发生早在ADR注射后24小时，而synaptopodin，一个功能性足细胞标记物，减少ADR注射后7天，与凋亡足细胞的数量显着增加。此外，来自过表达GFP-eNOS的小鼠微血管内皮细胞的条件培养基保护足细胞免受TNF-α诱导的突触足蛋白损失。总之，我们的研究表明，在ADR诱导的肾病中，内皮功能障碍和损伤先于足细胞损伤。肾小球内皮细胞可保护足细胞免受炎症损伤。了解肾小球内皮功能障碍在肾脏疾病发展中的作用将有助于设计治疗肾脏疾病的新策略。
The role of podocytes in the development and progression of glomerular disease has been extensively investigated in the past decade. However, the importance of glomerular endothelial cells in the pathogenesis of proteinuria and glomerulosclerosis has been largely ignored. Recent studies have demonstrated that endothelial nitric oxide synthatase (eNOS) deficiency exacerbates renal injury in anti-GBM and remnant kidney models and accelerates diabetic kidney damage. Increasing evidence also demonstrates the importance of the glomerular endothelium in preventing proteinuria. We hypothesize that endothelial dysfunction can initiate and promote the development and progression of glomerulopathy. Administration of adriamycin (ADR) to C57BL/6 mice, normally an ADR resistant strain, with an eNOS deficiency induced overt proteinuria, severe glomerulosclerosis, interstitial fibrosis and inflammation. We also examined glomerular endothelial cell and podocyte injury in ADR-induced nephropathy in Balb/c mice, an ADR susceptible strain, by immunostaining, TUNEL and Western blotting. Interestingly, down-regulation of eNOS and the appearance of apoptotic glomerular endothelial cells occurred as early as 24 hours after ADR injection, whilst synaptopodin, a functional podocyte marker, was reduced 7 days after ADR injection and coincided with a significant increase in the number of apoptotic podocytes. Furthermore, conditioned media from mouse microvascular endothelial cells over-expressing GFP-eNOS protected podocytes from TNF-α-induced loss of synaptopodin. In conclusion, our study demonstrated that endothelial dysfunction and damage precedes podocyte injury in ADR-induced nephropathy. Glomerular endothelial cells may protect podocytes from inflammatory insult. Understanding the role of glomerular endothelial dysfunction in the development of kidney disease will facilitate in the design of novel strategies to treat kidney disease.
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影响因子：
4.2
作者：
Kajiyama H;Titus S;Austin CP;Chiotos K;Matsumoto T;Sakairi T;Kopp JB
通讯作者：
Kopp JB
影响因子：
18.2
作者：
Greka A;Mundel P
通讯作者：
Mundel P
DOI：
10.1152/ajpgi.00069.2008
发表时间：
2008-07-01
影响因子：
4.5
作者：
Cogger, Victoria C.;Arias, Irwin M.;Le Couteur, David G.
通讯作者：
Le Couteur, David G.
影响因子：
20.1
作者：
Henke, Norbert;Schmidt-Ullrich, Ruth;Muller, Dominik N.
通讯作者：
Muller, Dominik N.
影响因子：
13.6
作者：
Jeansson, Marie;Bjorck, Karin;Haraldsson, Borje
通讯作者：
Haraldsson, Borje