%0 Journal Article
%T PPARgamma-Dependent Control of Renin Expression: Molecular Mechanisms and Pathophysiological Relevance
%A Vladimir T. Todorov
%J PPAR Research
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/451016
%X During the last years accumulating evidence demonstrated that the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) regulates the expression of renin gene and thus the overall renin production. This review summarizes the current knowledge of the transcriptional control of the renin gene by PPARgamma received from variety of models ranging from cell culture to transgenic animals. The molecular mechanisms of the PPARgamma action on renin are particularly interesting because they are featured by two newly described characteristics: one of them is the recently identified PPARgamma target sequence Pal3 which is specific for the human renin gene and mediates exceptionally high sensitivity to transactivation; the other is the potentiating effect of PPARgamma on the cAMP signaling in the renin-producing cells. Furthermore, I discuss the need for generating of additional transgenic animal models which are more appropriate with regard to the role of the PPARgamma-dependent regulation of the renin gene expression in human diseases such as arterial hypertension and metabolic syndrome. 1. Introduction Renin is aspartyl protease produced by the juxtaglomerular (JG) cells in the afferent arterioles of the kidney. It is the limiting enzyme in renin-angiotensin system (RAS), which plays crucial role in the control of blood pressure and salt excretion. The renin production is tightly regulated at the transcriptional level. Although the active renin is released into the circulation through regulated exocytosis, chronic (patho)physiological cues influencing the renin production (e.g., alterations in the salt intake, changes in the blood pressure, angiotensin II blockade, etc.) always induce parallel changes in the plasma renin concentration (PRC) and the renin mRNA levels in the JG cells [1]. Therefore, the control of the gene transcription is the decisive step in the overall regulation of the renin production. The cis-acting regulatory sequences of the renin gene are located in the 5¡¯-flanking promoter. The renin promoter has two evolutionary conserved regulatory regions: the proximal promoter which lies immediately upstream of the transcription starting site and the distal (or kidney) enhancer which consists of approximately 240£¿bp located at around £¿2.6£¿kb in the mouse and £¿12£¿kb in the human renin gene [2]. Many transcription factors acting through recognition sequences in the proximal promoter or the kidney enhancer are involved in the regulation of the renin gene [1]. Most of the experimental data on the function of these transcription
%U http://www.hindawi.com/journals/ppar/2013/451016/