The (pro)renin receptor in health and disease
The (pro)renin receptor in health and disease
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DOI：
10.3109/07853890903321567
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发表时间：
2010-01
影响因子：
4.4
通讯作者：
Genevieve Nguyen
中科院分区：
文献类型：
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作者：
Genevieve Nguyen
摘要 肾素 - 血管紧张素系统（RAS）是生理学和病理学中最重要的系统之一。（前）肾素受体（(P)RR）是该系统的一个新成分，作为潜在的新治疗靶点备受关注。该受体结合肾素以及肾素的无活性前酶形式——前肾素，这种结合会触发丝裂原活化蛋白激酶p42/p44的激活，进而上调促纤维化基因的表达。此外，与（P）RR结合的前肾素会发生构象变化并具有催化活性。许多动物研究试图证明（P）RR在高血压以及与糖尿病相关的组织损伤中的作用，虽然研究表明在患有肾小球硬化的糖尿病小鼠的肾脏以及患有心肌纤维化的高血压大鼠的心脏中发现（P）RR增加，但由于缺乏组织特异性（P）RR敲除的动物模型以及（P）RR拮抗剂，无法在（P）RR升高与心血管和肾脏疾病之间建立明确的联系。相反，人类和动物的突变使我们注意到（P）RR在早期发育，特别是神经元发育过程中的重要作用。
Abstract The renin-angiotensin system (RAS) is one of the most important systems in physiology and in pathology. The (pro)renin receptor ((P)RR) is a new component of the system that has attracted much attention being potentially a new therapeutic target. The receptor binds renin and the inactive proenzyme form of renin, prorenin, and the binding triggers the activation of the mitogen-activated protein kinase p42/p44 followed by up-regulation of the expression of profibrotic genes. In addition, prorenin bound to (P)RR undergoes a conformational change and becomes catalytically active. Many animal studies have tried to demonstrate a role for (P)RR in hypertension and in tissue damage associated with diabetes, but if they showed that increased (P)RR was found in kidney of diabetic mice associated with glomerulosclerosis and in heart of hypertensive rats associated with cardiac fibrosis, no definite link could be established between elevated (P)RR and cardiovascular and renal pathologies because of the absence of animal models with a tissue-specific (P)RR knock-out and a lack of a (P)RR antagonist. On the contrary, the human and the animal mutations are calling our attention to an essential role of (P)RR during early development, in particular in neuronal development.