Pan Li, Gross Kenneth W
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263-0001, USA.
Hypertension. 2005 Jan;45(1):3-8. doi: 10.1161/01.HYP.0000149717.55920.45. Epub 2004 Nov 15.
Renin, as a component of the renin-angiotensin system, plays important roles in the regulation of blood pressure, electrolyte homeostasis, and mammalian renal development. Transcription of renin genes is subject to complex developmental and tissue-specific regulation. Progress has been made recently in elucidating the molecular mechanisms involved in renin gene expression. Using mouse As4.1 cells, which have many features characteristic of the renin-expressing juxtaglomerular cells of kidney, a proximal promoter region (-197 to -50 bp) and an enhancer (-2866 to -2625 bp) have been identified in the mouse renin gene, Ren-1(c), that are critical for its expression. The proximal promoter region contains at least 7 transcription factor-binding sites, including a binding site for the products of Hox, developmental control genes. The enhancer consists of at least 11 transcription factor-binding sites and is responsive to various signal transduction pathways, including cAMP, retinoic acid, endothelin-1, and cytokines, to alter renin mRNA levels. Sequence highly homologous to the mouse enhancer is also found in the human and rat renin genes. How these regulatory regions function in vivo will be the focus of future study.
肾素作为肾素 - 血管紧张素系统的一个组成部分，在血压调节、电解质平衡以及哺乳动物肾脏发育过程中发挥着重要作用。肾素基因的转录受到复杂的发育和组织特异性调控。最近在阐明肾素基因表达所涉及的分子机制方面取得了进展。利用具有许多肾脏中表达肾素的球旁细胞特征的小鼠As4.1细胞，在小鼠肾素基因Ren-1(c)中鉴定出一个近端启动子区域（-197至-50 bp）和一个增强子（-2866至-2625 bp），它们对其表达至关重要。近端启动子区域包含至少7个转录因子结合位点，包括发育控制基因Hox产物的结合位点。增强子由至少11个转录因子结合位点组成，并对包括cAMP、视黄酸、内皮素-1和细胞因子在内的各种信号转导途径产生反应，以改变肾素mRNA水平。在人类和大鼠肾素基因中也发现了与小鼠增强子高度同源的序列。这些调控区域在体内如何发挥作用将是未来研究的重点。
