Institut de la Santé et de la Recherche Médicale, (INSERM) Unit 833 and Experimental Medicine Unit, Collège de France, 11 place Marcelin Berthelot, 75005, Paris, France.
Ann Med. 2010;42(1):13-8.
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.
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) 是系统的一个新组成部分，它作为一个新的治疗靶点引起了广泛关注。该受体结合肾素和无活性的肾素前体酶形式，即前肾素，结合触发丝裂原活化蛋白激酶 p42/p44 的激活，随后上调致纤维化基因的表达。此外，与 (P)RR 结合的前肾素发生构象变化并变得具有催化活性。许多动物研究试图证明 (P)RR 在高血压和与糖尿病相关的组织损伤中的作用，但由于缺乏具有组织特异性 (P)RR 敲除的动物模型和 (P)RR 拮抗剂，它们表明糖尿病小鼠肾脏中发现的 (P)RR 增加与肾小球硬化有关，高血压大鼠心脏中发现的 (P)RR 增加与心脏纤维化有关，因此不能确定升高的 (P)RR 与心血管和肾脏病变之间存在明确联系。相反，人类和动物的突变引起了我们对 (P)RR 在早期发育过程中的重要作用的关注，特别是在神经元发育过程中。
