Nguyen Geneviève, Burckle Céline A
INSERM U36, Pathologie vasculaire et endocrinologie rénale, 11 place Marcelin Berthelot, 75005, Paris.
Bull Acad Natl Med. 2004;188(4):621-8; discussion 628-9.
Our model of the renin-angiotensin system has become increasingly complex with the identification of new components and additional roles for angiotensin peptides and their receptors. A functional (pro)renin receptor has been cloned. It acts as (pro)renin co-factor on the cell surface, enhancing the efficiency of angiotensinogen cleavage by (pro)renin and unmasking prorenin catalytic activity. Binding of (pro)renin to the receptor mediates (pro)renin cellular effects by activating MAP kinases ERK1/2. Immunofluorescence studies have located the receptor on mesangial and vascular smooth-muscle cells in human heart and kidney. This suggests that the renin receptor may represent a mean of capturing (pro)renin from the circulation and concentrating it at the interface between smooth-muscle and endothelial cells. This recent discovery of a functional (pro)renin receptor forces the emergence of a new concept that casts renin as potentially playing a direct role in tissue damage, especially in situations where the tissue RAS is activated.
随着血管紧张素肽及其受体新成分的发现和其他作用的确定,我们的肾素-血管紧张素系统模型变得越来越复杂。一种功能性(前体)肾素受体已被克隆。它在细胞表面作为(前体)肾素辅因子,提高(前体)肾素裂解血管紧张素原的效率并揭示肾素原的催化活性。(前体)肾素与受体的结合通过激活丝裂原活化蛋白激酶ERK1/2介导(前体)肾素的细胞效应。免疫荧光研究已将该受体定位在人心脏和肾脏的系膜细胞和血管平滑肌细胞上。这表明肾素受体可能代表一种从循环中捕获(前体)肾素并将其浓缩在平滑肌和内皮细胞之间界面处的方式。最近对功能性(前体)肾素受体的这一发现促使一个新概念的出现,即肾素可能在组织损伤中发挥直接作用,尤其是在组织肾素-血管紧张素系统被激活的情况下。