PPARgamma-Dependent Control of Renin Expression: Molecular Mechanisms and Pathophysiological Relevance.

PPARgamma-Dependent Control of Renin Expression: Molecular Mechanisms and Pathophysiological Relevance.
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DOI:
10.1155/2013/451016
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发表时间:
2013
期刊:
影响因子:
2.9
通讯作者:
Todorov VT
Todorov VT
中科院分区:
医学3区
文献类型:
--
作者:
Todorov VT

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近年来越来越多的证据表明,核受体过氧化物酶体增殖物激活受体γ(PPARgamma)调控着肾素基因的表达,从而调节整个肾素的产生。本文综述了从细胞培养到转基因动物的各种模型中所获得的关于PPARgamma对肾素基因的转录调控的现有知识。PPARgamma作用于肾素的分子机制是特别有趣的,因为它们具有两个新描述的特征:其中之一是最近鉴定的PPARgamma靶序列Pal 3,其对人肾素基因具有特异性并介导对反式激活的异常高的敏感性;另一个是PPARgamma对产生肾素的细胞中cAMP信号传导的增强作用。此外,我讨论了需要产生额外的转基因动物模型,这是更合适的PPARgamma依赖性调节的肾素基因表达在人类疾病,如动脉高血压和代谢综合征的作用。
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.
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