Angiotensin converting enzyme in renal ontogeny: hypothesis for multiple roles

Jung, F; Bouyounes, Boutros T.; Barrio, Raquel; Tang, Shiow‐Shih; Diamant, Daniel; Ingelfinger, Julie R.

doi:10.1007/bf01213370

Cited by 28 publications

(13 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The developing metanephric kidney expresses all the components of the RAS (11,(21)(22)(23). The activity of the renal RAS is high during fetal and neonatal life and declines during postnatal maturation (22).…”

Section: Ontogeny Of Ace2mentioning

confidence: 99%

Ontogeny of angiotensin-converting enzyme 2

2011

View full text Add to dashboard Cite

INTRODUCTION:This study examined the temporal expression of angiotensin (ang)-converting enzyme 2 (ace2) during renal, heart, lung, and brain organogenesis in the mouse. RESULTS: We demonstrate that kidney ace2 mRNa levels are low on embryonic day (e) 12.5, increase fourfold during development, and decline in adulthood. In extrarenal tissues, ace2 mRNa levels are also low during early gestation, increase in perinatal period, and peak in adulthood. The lung shows the highest age-related increase in ace2 mRNa levels followed by the brain, kidney, and heart. ace2 protein levels and enzymatic activity are high in all organs studied during gestation and decline postnatally. ang II decreases ace2 mRNa levels and enzymatic activity in kidneys grown ex vivo. These effects of ang II are blocked by the specific ang II aT 1 receptor (aT 1 R) antagonist candesartan, but not by the aT 2 receptor (aT 2 R) antagonist PD123319. DISCUSSION: We conclude that ACE2 gene and protein expression and enzymatic activity are developmentally regulated in a tissue-specific manner. ang II, acting through aT 1 R, exerts a negative feedback on ace2 during kidney development. We postulate that relatively high ace2 protein levels and enzymatic activity observed during gestation may play a role in kidney, lung, brain, and heart organogenesis.

show abstract

Section: Ontogeny Of Ace2mentioning

confidence: 99%

Ontogeny of angiotensin-converting enzyme 2

2011

View full text Add to dashboard Cite

show abstract

“…Similar to angiotensinogen, renin expression reaches a peak around birth (4). In the rat kidney, ACE can be detected at E16, and AT-1 and AT-2 receptors are expressed throughout metanephric development (5)(6)(7). Consequently, all the components of the RAS are expressed during early kidney development in specific temporal-spatial patterns associated with nephrogenesis, suggesting the RAS may play an important role during renal development.…”

mentioning

confidence: 99%

Genetic Evidence That Lethality in Angiotensinogen-deficient Mice Is Due to Loss of Systemic but Not Renal Angiotensinogen

Ding¹,

Stec²

2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

Angiotensinogen (AGT)-deficient mice die shortly after birth presumably due to renal dysfunction caused by the presence of severe vascular and tubular lesions in the kidney. Because AGT is expressed in renal proximal tubule cells, we hypothesized that its loss may be the primary mediator of the lethal phenotype. We generated two models to test this hypothesis by breeding transgenic mice expressing human renin with mice expressing human AGT (hAGT) either systemically or kidneyspecifically. We then bred double transgenic mice with AGT؉/؊ mice, intercrossed the compound heterozygotes, and examined the offspring. We previously reported that the presence of the human renin and systemically expressed hAGT transgene complemented the lethality observed in AGT؊/؊ mice. On the contrary, we show herein that the presence of the human renin and kidney-specific hAGT transgene cannot rescue lethality in AGT؊/؊ mice. An analysis of newborns indicated that AGT؊/؊ mice were born in normal numbers, and collection of dead 10-day old pups revealed an enrichment in AGT؊/؊. Importantly, we demonstrated that angiotensinogen protein and functional angiotensin II was generated in the kidney, and the kidney-specific transgene was temporally expressed during renal development similar to the endogenous AGT gene. These data strongly support the notion that the loss of systemic AGT, but not intrarenal AGT, is responsible for death in the AGT؊/؊ mouse model. Taken together with our previous studies, we conclude that the intrarenal reninangiotensin system located in the proximal tubule plays an important role in blood pressure regulation and may cause hypertension if overexpressed, but may not be required for continued development of the kidney after birth.

show abstract

“…The developing metanephros expresses all of the components of the RAS (Table 1) [25,26,27,28,29,30]. The activity of the renal RAS is high during fetal and The nephric duct is formed from the intermediate mesoderm and extends caudally to induce adjacent mesoderm to differentiate into two transient kidney types, pronephros and mesonephros.…”

Section: Expression Of the Ras Components In The Developing Kidneymentioning

confidence: 99%

Role of the renin-angiotensin system in the development of the ureteric bud and renal collecting system

Yosypiv

El‐Dahr

2005

Pediatr Nephrol

View full text Add to dashboard Cite

Genetic, biochemical and physiological studies have demonstrated that the renin-angiotensin system (RAS) plays a fundamental role in kidney development. All of the components of the RAS are expressed in the metanephros. Mutations in the genes encoding components of the RAS in mice or pharmacological inhibition of RAS in animals or humans cause diverse congenital abnormalities of the kidney and lower urinary tract. The latter include renal vascular abnormalities, abnormal glomerulogenesis, renal papillary hypoplasia, hydronephrosis, aberrant UB budding, duplicated collecting system, and urinary concentrating defect. Thus, the actions of angiotensin (ANG) II during kidney development are pleiotropic both spatially and temporally. Whereas the role of ANG II in renovascular and glomerular development has received much attention, little is known about the potential role of ANG II and its receptors in the morphogenesis of the collecting system. In this review, we discuss recent genetic and functional evidence gathered from transgenic knockout mice and in vitro organ and cell culture implicating the RAS in the development of the ureteric bud and collecting ducts. A novel conceptual framework has emerged from this body of work which states that stroma-derived ANG II elicits activation of AT(1)/AT(2) receptors expressed on the ureteric bud to stimulate branching morphogenesis as well as collecting duct elongation and papillogenesis.

show abstract

Angiotensin converting enzyme in renal ontogeny: hypothesis for multiple roles

Cited by 28 publications

References 64 publications

Ontogeny of angiotensin-converting enzyme 2

Ontogeny of angiotensin-converting enzyme 2

Genetic Evidence That Lethality in Angiotensinogen-deficient Mice Is Due to Loss of Systemic but Not Renal Angiotensinogen

Role of the renin-angiotensin system in the development of the ureteric bud and renal collecting system

Contact Info

Product

Resources

About