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通过RNA干扰选择性沉默血管紧张素受体1a亚型(AT1aR)

Selective silencing of angiotensin receptor subtype 1a (AT1aR) by RNA interference.

作者信息

Vázquez Jorge, Correa de Adjounian María F, Sumners Colin, González Aaron, Diez-Freire Carlos, Raizada Mohan K

机构信息

Department of Physiology and Functional Genomics, College of Medicine, University of Florida, McKnight Brain Institute, Gainesville, FL 32610, USA.

出版信息

Hypertension. 2005 Jan;45(1):115-9. doi: 10.1161/01.HYP.0000150161.78556.c6. Epub 2004 Nov 29.

DOI:10.1161/01.HYP.0000150161.78556.c6
PMID:15569855
Abstract

Angiotensin II exerts its physiological effects by activating multiple subtypes of its receptor such as AT1a-, AT1b-, and AT2-receptors. Because of a high degree of similarity among these G-protein-coupled receptors, it has been difficult to assign diverse physiological actions of angiotensin II through these receptor subtypes. We have developed small interfering RNAs to selectively inhibit the expression of the AT1a receptor (AT1aR) subtype. A dsRNA, AT1 47, was found to be highly selective and efficient in reducing the levels of AT1aR subtype. Transfection of AT1aR-expressing CHO cells with dsRNA AT1 47 resulted in an 80% decrease in the AT1aR expression. In contrast, dsRNA AT1 47 showed no significant effects on both AT1bR and AT2R subtypes. Thus, AT1 47 provides us with a powerful tool to selectively silence this subtype of receptor to investigate its role in cardiovascular physiology.

摘要

血管紧张素II通过激活其多种受体亚型(如AT1a、AT1b和AT2受体)发挥其生理作用。由于这些G蛋白偶联受体之间具有高度相似性,因此很难通过这些受体亚型来区分血管紧张素II的多种生理作用。我们已开发出小干扰RNA,以选择性抑制AT1a受体(AT1aR)亚型的表达。发现双链RNA(dsRNA)AT1 47在降低AT1aR亚型水平方面具有高度选择性和高效性。用dsRNA AT1 47转染表达AT1aR的CHO细胞,导致AT1aR表达下降80%。相比之下,dsRNA AT1 47对AT1bR和AT2R亚型均无显著影响。因此,AT1 47为我们提供了一种强大的工具,可选择性沉默该受体亚型,以研究其在心血管生理学中的作用。

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