García-Villalba Pilar, Denkers Nathaniel D, Wittwer Carl T, Hoff Charles, Nelson Raoul D, Mauch Teri Jo
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84132-2204, USA.
Nephron Exp Nephrol. 2003;94(4):e154-9. doi: 10.1159/000072499.
BACKGROUND/AIMS: Angiotensin II (Ang II) is an important growth factor in the fetal kidney. Molecular cloning and pharmacological studies have defined two major classes of Ang II receptors designated AT1 and AT2. Two AT1 isoforms, AT1A and AT1B, exist in rodents. AT1 promotes growth and proliferation and mediates many of the known physiological actions of Ang II. AT2 appears to antagonize AT1. Our goal was to measure their relative contributions to Ang II signaling in the developing kidney.
We used real-time RT-PCR to quantify AT1A, AT1B, AT2 and the housekeeping gene EF1alpha mRNA in kidneys from embryonic (E) day 14-20 and postnatal (P) day 1-14 rats.
AT2 mRNA declined from 1.4 x 10(4) copies/10(6) copies EF1alpha on E14 to 4.2 x 10(3) copies/10(6) copies EF1alpha on P14. In contrast, total AT1 mRNA increased gradually from 2.0 x 10(3) copies/10(6) copies EF1alpha on E14 to 2.0 x 10(4) copies/10(6) copies EF1alpha on P14, with AT1A accounting for about 90% of total AT1 mRNA throughout nephrogenesis. Moreover, the ratio of AT2/(AT1A + AT1B) decreased in a log-linear fashion during maturation, from 6.7 on E14 to 0.2 on P14.
The ratio of AT2 to AT1 gene expression modulates Ang II action in the developing kidney.
背景/目的：血管紧张素II（Ang II）是胎儿肾脏中的一种重要生长因子。分子克隆和药理学研究已确定了两类主要的Ang II受体，分别命名为AT1和AT2。啮齿动物中存在两种AT1亚型，即AT1A和AT1B。AT1促进生长和增殖，并介导Ang II的许多已知生理作用。AT2似乎拮抗AT1。我们的目标是测量它们在发育中的肾脏中对Ang II信号传导的相对贡献。
我们使用实时逆转录聚合酶链反应（RT-PCR）来定量胚胎（E）第14至20天和出生后（P）第1至14天大鼠肾脏中AT1A、AT1B、AT2和管家基因EF1α的mRNA。
AT2 mRNA从E14时的1.4×10⁴拷贝/10⁶拷贝EF1α下降到P14时的4.2×10³拷贝/10⁶拷贝EF1α。相比之下，总AT1 mRNA从E14时的2.0×10³拷贝/10⁶拷贝EF1α逐渐增加到P14时的2.0×10⁴拷贝/10⁶拷贝EF1α，在整个肾发生过程中，AT1A约占总AT1 mRNA 的90%。此外，在成熟过程中，AT2/（ATIA + AT1B）的比值呈对数线性下降，从E14时的6.7降至P14时的0.2。
AT2与AT1基因表达的比值调节发育中肾脏的Ang II作用。
