Institut de la Santé et de la Recherche Médicale, Collège de France, Paris, France.
J Am Soc Nephrol. 2010 Jan;21(1):18-23. doi: 10.1681/ASN.2009030300. Epub 2009 Nov 16.
The (pro)renin receptor (PRR) binds renin and prorenin, its proenzyme inactive form. Receptor-bound prorenin becomes enzymatically active and binding then activates the MAP kinases ERK1/2 and p38 pathways, leading to upregulation of profibrotic and cyclooxygenase-2 genes independent of angiotensin II generation. These characteristics explain the interest in the potential role of PRR in organ damage in diseases associated with activation of the renin-angiotensin system (RAS), in particular hypertension and diabetes. Although identification of PRR has improved our understanding of the physiology of the tissue RAS, its role in pathology is far from clear. Transgenic animals overexpressing PRR ubiquitously or selectively in smooth-muscle cells develop high BP or glomerulosclerosis, and increased expression of PRR is reported in models of hypertension or kidney damage. However, definitive proof is still lacking for a role for PRR in disease, or by showing improvement of disease by tissue-specific ablation of PRR or by administration of a specific PRR antagonist. Furthermore, the early embryonic lethality seen in PRR-null mice suggests PRR has additional essential cellular functions we do not understand.
（前）肾素受体（PRR）结合肾素和前肾素，即其无活性的酶原形式。受体结合的前肾素变得具有酶活性，结合后激活 MAP 激酶 ERK1/2 和 p38 途径，导致独立于血管紧张素 II 产生的促纤维化和环氧化酶-2 基因的上调。这些特征解释了 PRR 在与肾素-血管紧张素系统（RAS）激活相关的疾病中的器官损伤中的潜在作用的意义，特别是在高血压和糖尿病中。尽管 PRR 的鉴定提高了我们对组织 RAS 生理学的理解，但它在病理学中的作用还远不清楚。在平滑肌细胞中广泛或选择性过表达 PRR 的转基因动物会发展出高血压或肾小球硬化，并且在高血压或肾脏损伤模型中报告了 PRR 表达增加。然而，仍然缺乏 PRR 在疾病中的作用的明确证据，或者通过显示通过组织特异性消融 PRR 或通过施用特定的 PRR 拮抗剂来改善疾病。此外，PRR 敲除小鼠中观察到的早期胚胎致死性表明 PRR 具有我们不理解的其他必需的细胞功能。
