Terada Tomomasa, Urushihara Maki, Saijo Takahiko, Nakagawa Ryuji, Kagami Shoji
Department of Pediatrics, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-cho 3-18-15, Tokushima, 770-8503, Japan.
Eur J Pediatr. 2017 Feb;176(2):183-189. doi: 10.1007/s00431-016-2820-9. Epub 2016 Dec 19.
Although a recent study demonstrated that the (pro)renin receptor ((P)RR) was highly expressed in the developing kidney during the mouse embryonic development, the mechanism by which (P)RR supports renal development in humans is not fully understood. In this study, we examined the plasma levels of (pro)renin and soluble (P)RR (s(P)RR) in cord blood and neonates as well as (P)RR expression in human kidney tissues. Samples were collected from 57 preterm and 67 full-term human neonates. (Pro)renin and s(P)RR levels were measured using enzyme-linked immunosorbent assays. Additionally, we performed an immunohistochemical (IHC) analysis of kidney tissues from neonates and minor glomerular abnormalities in order to assess (P)RR expression in the kidney. Plasma (pro)renin and s(P)RR levels in cord blood were significantly higher in preterm neonates than in full-term neonates. Four weeks after birth, these differences were no longer evident for either plasma (pro)renin or s(P)RR levels between the two groups. Importantly, plasma (pro)renin and s(P)RR levels in cord blood were inversely correlated with gestational age. Furthermore, IHC indicated that renal expression levels of (P)RR in neonates were stronger than those in minor glomerular abnormalities.
(P)RR may play a pivotal role in prenatal renal development in humans. What is Known: • Renal renin-angiotensin system (RAS) has several pathophysiologic functions not only in blood pressure regulation but also in pediatric renal disease. • Renal RAS activation plays a key role of renal development during gestation. What is New : • Plasma (pro)renin and soluble (pro)renin receptor (s(P)RR) levels in cord blood were significantly higher in preterm neonates than in full-term neonates. • Immunohistochemical analysis of kidney tissue indicated that renal expression levels of (P)RR in neonates were stronger than in minor glomerular abnormalities.
尽管最近一项研究表明，（前）肾素受体（(P)RR）在小鼠胚胎发育期间的发育中的肾脏中高度表达，但(P)RR支持人类肾脏发育的机制尚未完全了解。在本研究中，我们检测了脐血和新生儿中（前）肾素和可溶性(P)RR（s(P)RR）的血浆水平以及人类肾脏组织中(P)RR的表达。样本取自57例早产儿和67例足月儿。使用酶联免疫吸附测定法测量（前）肾素和s(P)RR水平。此外，我们对新生儿肾脏组织和轻度肾小球异常进行了免疫组织化学（IHC）分析，以评估肾脏中(P)RR的表达。脐血中血浆（前）肾素和s(P)RR水平在早产儿中显著高于足月儿。出生四周后，两组之间血浆（前）肾素或s(P)RR水平的这些差异不再明显。重要的是，脐血中血浆（前）肾素和s(P)RR水平与胎龄呈负相关。此外，免疫组织化学表明，新生儿中(P)RR的肾脏表达水平强于轻度肾小球异常中的表达水平。
(P)RR可能在人类产前肾脏发育中起关键作用。
• 肾脏肾素-血管紧张素系统（RAS）不仅在血压调节中，而且在儿科肾脏疾病中具有多种病理生理功能。
• 肾脏RAS激活在妊娠期间肾脏发育中起关键作用。
• 脐血中血浆（前）肾素和可溶性（前）肾素受体（s(P)RR）水平在早产儿中显著高于足月儿。
• 肾脏组织的免疫组织化学分析表明，新生儿中(P)RR的肾脏表达水平强于轻度肾小球异常中的表达水平。
