Genetic deletion of the angiotensin-(1-7) receptor Mas leads to glomerular hyperfiltration and microalbuminuria
Genetic deletion of the angiotensin-(1-7) receptor Mas leads to glomerular hyperfiltration and microalbuminuria
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DOI：
10.1038/ki.2009.61
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发表时间：
2009-06-01
影响因子：
19.6
通讯作者：
Simoes e Silva, Ana Cristina
中科院分区：
文献类型：
--
作者：
Pinheiro, Sergio V. B.;Ferreira, Anderson J.;Simoes e Silva, Ana Cristina
血管紧张素-(1-7)是血管紧张素I和血管紧张素II的活性片段，通常与血管紧张素II的血管和增殖作用相反。在这里，我们用Mas敲除小鼠来评估血管紧张素-(1-7)受体Mas对肾脏生理和形态的影响。与野生型动物相比，Mas基因敲除小鼠的尿量和钠排泄量显著减少，但自由水清除率没有显著变化。显著增高的菊粉清除率和伴随肾血流量减少的微量白蛋白尿表明，在基因敲除小鼠中发生了肾小球高滤过。组织学分析发现肾小球簇直径减小，系膜和间质中IV型胶原和纤维连接蛋白表达增加，间质中III型胶原表达增加。基因敲除小鼠的这些纤维化改变和肾功能障碍与血管紧张素II AT1受体和转化生长因子β mRNA的上调有关。我们的研究表明，Mas通过控制肾脏血管紧张素II AT1受体转导的作用，作为肾纤维化的关键调节剂。肾脏国际（2009）75,1184-1193；doi: 10.1038 /吻。2009.61;2009年3月4日在线发布
Angiotensin-(1-7), an active fragment of both angiotensins I and II, generally opposes the vascular and proliferative actions of angiotensin II. Here we evaluated effects of the angiotensin-(1-7) receptor Mas on renal physiology and morphology using Mas-knockout mice. Compared to the wild-type animals, Mas knockout mice had significant reductions in urine volume and fractional sodium excretion without any significant change in free-water clearance. A significantly higher inulin clearance and microalbuminuria concomitant with a reduced renal blood flow suggest that glomerular hyperfiltration occurs in the knockout mice. Histological analysis found reduced glomerular tuft diameter and increased expression of collagen IV and fibronectin in the both the mesangium and interstitium, along with increased collagen III in the interstitium. These fibrogenic changes and the renal dysfunction of the knockout mice were associated with an upregulation of angiotensin II AT1 receptor and transforming growth factor-beta mRNA. Our study suggests that Mas acts as a critical regulator of renal fibrogenesis by controlling effects transduced through angiotensin II AT1 receptors in the kidney. Kidney International (2009) 75, 1184-1193; doi:10.1038/ki. 2009.61; published online 4 March 2009