Molecular Mechanisms of Hypertensive Nephropathy: Renoprotective Effect of Losartan through Hsp70.
Molecular Mechanisms of Hypertensive Nephropathy: Renoprotective Effect of Losartan through Hsp70.
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DOI：
10.3390/cells10113146
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发表时间：
2021-11-12
期刊：
影响因子：
6
通讯作者：
Vallés PG
中科院分区：
文献类型：
--
作者：
Costantino VV;Gil Lorenzo AF;Bocanegra V;Vallés PG
高血压肾硬化是继糖尿病之后导致终末期肾病的第二常见原因。多年来，高血压肾病一直关注传入小动脉和肾小球损伤以及肾素血管紧张素系统（RAS）的参与。尽管如此，近年来，新的证据表明，持续的高血压会损伤肾小管细胞，导致上皮间质转化（EMT）和肾小管间质纤维化。主要由高血压引起的肾小球水平损伤会引起肾小球后肾小管周围毛细血管的变化，进而引起内皮损伤和缺氧。微血管功能障碍，通过诱导缺氧环境，引发炎症、EMT、上皮细胞去分化和纤维化。高血压肾病还包括足细胞消失和丢失，导致滤过屏障破坏。本综述重点介绍了高血压肾病病理生理学中涉及的分子机制和组织学方面，并结合了有关 EMT 和肾小管间质纤维化的知识。讨论了 Hsp70 伴侣在血管紧张素 II 1 型受体 (AT1R) 阻断后血管紧张素 II 诱导的 EMT 中的作用，作为抗高血压肾损伤治疗策略的可能分子靶点。
Hypertensive nephrosclerosis is the second most common cause of end-stage renal disease after diabetes. For years, hypertensive kidney disease has been focused on the afferent arterioles and glomeruli damage and the involvement of the renin angiotensin system (RAS). Nonetheless, in recent years, novel evidence has demonstrated that persistent high blood pressure injures tubular cells, leading to epithelial–mesenchymal transition (EMT) and tubulointerstitial fibrosis. Injury primarily determined at the glomerular level by hypertension causes changes in post-glomerular peritubular capillaries that in turn induce endothelial damage and hypoxia. Microvasculature dysfunction, by inducing hypoxic environment, triggers inflammation, EMT with epithelial cells dedifferentiation and fibrosis. Hypertensive kidney disease also includes podocyte effacement and loss, leading to disruption of the filtration barrier. This review highlights the molecular mechanisms and histologic aspects involved in the pathophysiology of hypertensive kidney disease incorporating knowledge about EMT and tubulointerstitial fibrosis. The role of the Hsp70 chaperone on the angiotensin II–induced EMT after angiotensin II type 1 receptor (AT1R) blockage, as a possible molecular target for therapeutic strategy against hypertensive renal damage is discussed.
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影响因子：
3.2
作者：
Farris AB;Colvin RB
通讯作者：
Colvin RB
DOI：
10.1056/nejmoa0910975
发表时间：
2010-09-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Appel LJ;Wright JT Jr;Greene T;Agodoa LY;Astor BC;Bakris GL;Cleveland WH;Charleston J;Contreras G;Faulkner ML;Gabbai FB;Gassman JJ;Hebert LA;Jamerson KA;Kopple JD;Kusek JW;Lash JP;Lea JP;Lewis JB;Lipkowitz MS;Massry SG;Miller ER;Norris K;Phillips RA;Pogue VA;Randall OS;Rostand SG;Smogorzewski MJ;Toto RD;Wang X;AASK Collaborative Research Group
通讯作者：
AASK Collaborative Research Group
影响因子：
3.6
作者：
Chandel N;Ayasolla K;Wen H;Lan X;Haque S;Saleem MA;Malhotra A;Singhal PC
通讯作者：
Singhal PC
影响因子：
4.9
作者：
Bocanegra, Victoria;Manucha, Walter;Valles, Patricia G.
通讯作者：
Valles, Patricia G.
影响因子：
2.7
作者：
Burns, W. C.;Thomas, M. C.
通讯作者：
Thomas, M. C.