Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA, USA.
Pediatr Res. 2013 Jul;74(1):5-10. doi: 10.1038/pr.2013.63. Epub 2013 Apr 10.
This study examined temporal expression of the (pro)renin receptor ((P)RR), during renal, heart, lung, and brain organogenesis in the mouse.
(P)RR expression was determined by quantitative reverse-transcription PCR, western blotting, and immunohistochemistry.
Brain, kidney, and lung (P)RR mRNA levels increased progressively during gestation and peak on postnatal day (P)10. (P)RR protein contents were high during gestation in all organs studied and declined with maturation. Brain (P)RR was expressed most prominently in the ependymal lining of the ventricles. In the embryonic day (E)16.5 and E18.5 metanephros, (P)RR was present in the ureteric bud and ureteric bud-derived collecting ducts. In the fetal heart, (P)RR was expressed diffusely in the myocardium, whereas pulmonary (P)RR was detected at highest levels in the epithelium of branching airways. Treatment of newborn kidneys with the angiotensin (Ang) II type 1 receptor (AT₁R) antagonist candesartan increased (P)RR mRNA levels.
(P)RR gene and protein expressions in the brain, kidney, heart, and lung are developmentally regulated in a tissue-specific manner. Endogenous Ang II, acting via the AT₁R, exerts a negative feedback on (P)RR in the newborn kidney. These findings suggest that high (P)RR protein levels observed during gestation may play a role in brain, kidney, heart, and lung organogenesis.
本研究检测了(前)肾素受体((P)RR)在小鼠肾脏、心脏、肺和脑器官发生过程中的时间表达。
通过定量逆转录 PCR、western blot 和免疫组织化学检测(P)RR 的表达。
脑、肾和肺(P)RR mRNA 水平在妊娠期间逐渐增加,在出生后第 10 天(P)10 达到峰值。在所有研究的器官中,(P)RR 蛋白含量在妊娠期间较高,并随成熟而下降。脑(P)RR 在脑室的室管膜衬里中表达最为明显。在胚胎第 16.5 天和 18.5 天的后肾中,(P)RR 存在于输尿管芽和输尿管芽衍生的集合管中。在胎儿心脏中,(P)RR 在心肌中广泛表达,而肺(P)RR 在分支气道的上皮中表达水平最高。用血管紧张素(Ang)II 型 1 受体(AT₁R)拮抗剂坎地沙坦处理新生肾脏可增加(P)RR mRNA 水平。
脑、肾、心和肺中(P)RR 基因和蛋白的表达以组织特异性方式在发育过程中受到调节。内源性 Ang II 通过 AT₁R 对新生儿肾脏中的(P)RR 发挥负反馈作用。这些发现表明,在妊娠期间观察到的高(P)RR 蛋白水平可能在脑、肾、心和肺器官发生中发挥作用。