Rosiglitazone treatment of type 2 diabetic db/db mice attenuates urinary albumin and angiotensin converting enzyme 2 excretion.
Rosiglitazone treatment of type 2 diabetic db/db mice attenuates urinary albumin and angiotensin converting enzyme 2 excretion.
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DOI：
10.1371/journal.pone.0062833
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Elased KM
中科院分区：
文献类型：
--
作者：
Chodavarapu H;Grobe N;Somineni HK;Salem ES;Madhu M;Elased KM
肾脏血管紧张素系统的变化在心血管和肾脏疾病的发生和进展中发挥着关键作用。血管紧张素转换酶2（ACE 2）在肾小管中高度表达，并已被证明在糖尿病中具有肾脏保护作用。该蛋白酶是一种去整合素和金属蛋白酶（ADAM）17，参与包括ACE 2在内的几种跨膜蛋白的胞外域脱落。与对照组相比，db/db小鼠的肾脏ACE 2和ADAM 17显著增加。我们研究了胰岛素增敏剂罗格列酮对db/db糖尿病小鼠白蛋白尿、肾脏ADAM 17蛋白表达和ACE 2脱落的影响。罗格列酮治疗db/db小鼠使高血糖症正常化，减轻肾损伤并降低尿ACE 2和肾ADAM 17蛋白表达。尿排泄的ACE 2具有酶活性。尿ACE 2蛋白质印迹分析显示两个突出的免疫反应性条带，约70和90 kDa。主要的免疫反应性条带比肾脏裂解物显示的条带短约20 kDa，表明尿液中活性肾脏ACE 2的可能胞外域脱落。因此，很容易推测罗格列酮的肾脏保护作用可能部分通过下调肾脏ADAM 17和ACE 2脱落来介导。此外，血糖、尿白蛋白、血浆胰高血糖素和甘油三酯水平与尿ACE 2排泄呈正相关。结论：尿ACE 2可作为糖尿病肾病的敏感生物标志物，并可用于监测肾脏保护药物的有效性。
Alterations within the renal renin angiotensin system play a pivotal role in the development and progression of cardiovascular and renal disease. Angiotensin converting enzyme 2 (ACE2) is highly expressed in renal tubules and has been shown to be renoprotective in diabetes. The protease, a disintegrin and metalloprotease (ADAM) 17, is involved in the ectodomain shedding of several transmembrane proteins including ACE2. Renal ACE2 and ADAM17 were significantly increased in db/db mice compared to controls. We investigated the effect of the insulin sensitizer, rosiglitazone, on albuminuria, renal ADAM17 protein expression and ACE2 shedding in db/db diabetic mice. Rosiglitazone treatment of db/db mice normalized hyperglycemia, attenuated renal injury and decreased urinary ACE2 and renal ADAM17 protein expression. Urinary excreted ACE2 is enzymatically active. Western blot analysis of urinary ACE2 demonstrated two prominent immunoreactive bands at approximately 70 & 90 kDa. The predominant immunoreactive band is approximately 20 kDa shorter than the one demonstrated for kidney lysate, indicating possible ectodomain shedding of active renal ACE2 in the urine. Therefore, it is tempting to speculate that renoprotection of rosiglitazone could be partially mediated via downregulation of renal ADAM17 and ACE2 shedding. In addition, there was a positive correlation between blood glucose, urinary albumin, plasma glucagon, and triglyceride levels with urinary ACE2 excretion. In conclusion, urinary ACE2 could be used as a sensitive biomarker of diabetic nephropathy and for monitoring the effectiveness of renoprotective medication.
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影响因子：
158.5
作者：
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通讯作者：
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DOI：
10.2353/ajpath.2006.051091
发表时间：
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期刊：
The American journal of pathology
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DOI：
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发表时间：
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影响因子：
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