Renin Cells Are Precursors for Multiple Cell Types that Switch to the Renin Phenotype When Homeostasis Is Threatened

López, María Luisa S. Sequeira; Pentz, Ellen S.; Nomasa, Takayo; Smithies, Oliver; Gómez, R. Ariel

doi:10.1016/s1534-5807(04)00134-0

Cited by 237 publications

(206 citation statements)

References 22 publications

(7 reference statements)

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“…Although more than one renin gene exists in mice, we believe that the expression pattern of the mouse renin-1d gene, which was used as a reporter in this study, is very similar to the expression of the human renin gene. 16,17 As anticipated, pVHL knockdown resulted in constitutive stabilization of HIF in renin-expressing cells in afferent arterioles and collecting ducts. The activation of the renin promoter in the collecting duct during kidney development is a known but unexplained phenomenon.…”

Section: Discussionsupporting

confidence: 61%

“…16 Animals were kept under standard housing conditions with a 12:12-hour light:dark cycle and food (NaCl 0.6%; Ssniff, Soest, Germany) and water ad libitum. Stimulation of the RAS was induced by feeding a low-salt diet (NaCl 0.02%; Ssniff) combined with the ACE inhibitor enalapril (on average, 10 mg/kg per day) added to the drinking water for 3 weeks.…”

Section: Animalsmentioning

confidence: 99%

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Deletion of von Hippel–Lindau Protein Converts Renin-Producing Cells into Erythropoietin-Producing Cells

Kurt

Paliege

Willam

et al. 2013

Journal of the American Society of Nephrology

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States of low perfusion pressure of the kidney associate with hyperplasia or expansion of renin-producing cells, but it is unknown whether hypoxia-triggered genes contribute to these changes. Here, we stabilized hypoxia-inducible transcription factors (HIFs) in mice by conditionally deleting their negative regulator, Vhl, using the Cre/loxP system with renin-1d promoter-driven Cre expression. Vhl 2/2REN mice were viable and had normal BP. Deletion of Vhl resulted in constitutive accumulation of HIF-2a in afferent arterioles and glomerular cells and HIF-1a in collecting duct cells of the adult kidney. The preglomerular vascular tree developed normally, but far fewer renin-expressing cells were present, with more than 70% of glomeruli not containing renin cells at the typical juxtaglomerular position. Moreover, these mice had an attenuated expansion of renin-producing cells in response to a low-salt diet combined with an ACE inhibitor. However, renin-producing cells of Vhl 2/2REN mice expressed the erythropoietin gene, and they were markedly polycythemic. Taken together, these results suggest that hypoxia-inducible genes, regulated by VHL, are essential for normal development and physiologic adaptation of renin-producing cells. In addition, deletion of Vhl shifts the phenotype of juxtaglomerular cells from a renin-to erythropoietin-secreting cell type, presumably in response to HIF-2 accumulation.

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Section: Discussionsupporting

confidence: 61%

Section: Animalsmentioning

confidence: 99%

Deletion of von Hippel–Lindau Protein Converts Renin-Producing Cells into Erythropoietin-Producing Cells

Kurt

Paliege

Willam

et al. 2013

Journal of the American Society of Nephrology

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“…In adult mammals, low Na ϩ or RAS inhibition by angiotensin-converting enzyme (ACE) inhibitors, such as captopril, upregulate ren mRNA and renin protein (21,80). In combination, low salinity and captopril result in juxtaglomerular cell hypertrophy and renin cell recruitment along renal arterioles (7,18,36,67). Blockade of the RAS cascade arrests the ANG II-mediated negative feedback loop regulating ren transcription and renin cell recruitment (36).…”

Section: Larval Fish Renin Characterizationmentioning

confidence: 99%

“…Adult renin-expressing cells are restricted to the juxtaglomerular apparatus and play a vital role in ion homeostasis by secreting activated renin enzyme via cytoplasmic granules (17,31,36,63). Upon physiological challenge by RAS inhibition or low Na ϩ , prearteriolar vascular smooth muscle cells (VSMC) reestablish their embryonic renin phenotype (67), a process dependent on Notch (61) and endothelial nitric oxide (51).…”

mentioning

confidence: 99%

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

Rider

Mullins

Verdon

et al. 2015

American Journal of Physiology-Renal Physiology

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Rider SA, Mullins LJ, Verdon RF, MacRae CA, Mullins JJ. Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium. Am J Physiol Renal Physiol 309: F531-F539, 2015. First published July 22, 2015 doi:10.1152/ajprenal.00247.2015.-Although renin is a critical regulatory enzyme of the cardiovascular system, its roles in organogenesis and the establishment of cardiovascular homeostasis remain unclear. Mammalian renin-expressing cells are widespread in embryonic kidneys but are highly restricted, specialized endocrine cells in adults. With a functional pronephros, embryonic zebrafish are ideal for delineating the developmental functions of renin-expressing cells and the mechanisms governing renin transcription. Larval zebrafish renin expression originates in the mural cells of the juxtaglomerular anterior mesenteric artery and subsequently at extrarenal sites. The role of renin was determined by assessing responses to renin-angiotensin system blockade, salinity variation, and renal perfusion ablation. Renin expression did not respond to renal flow ablation but was modulated by inhibition of angiotensin-converting enzyme and altered salinity. Our data in larval fish are consistent with conservation of renin's physiological functions. Using transgenic renin reporter fish, with mindbomb and cloche mutants, we show that Notch signaling and the endothelium are essential for developmental renin expression. After inhibition of angiogenesis, renin-expressing cells precede angiogenic sprouts. Arising from separate lineages, but relying on mutual interplay with endothelial cells, renin-expressing cells are among the earliest mural cells observed in larval fish, performing both endocrine and paracrine functions. renin; zebrafish; notch; endothelium; angiogenesis RENIN is the rate-limiting enzyme of the renin-angiotensin system (RAS). Mammalian ANG II, the effector of the RAS, is principally involved in blood pressure homeostasis by regulation of vasomotor tone and Na ϩ retention. ANG II also regulates cell proliferation and angiogenesis (12,22). Pathological activation of the RAS is associated with cardiovascular diseases, including hypertension and heart failure, and is consequently a major target of therapeutic agents (11).Renin and its cognate cells are required for normal renal development (2), including angiogenesis of the renal vascular tree (59). In mice, ablation of the renin gene or renin-expressing cells leads to renal developmental abnormalities (55,71,79). The vasculature of mammalian embryonic kidneys have a transient but extensive coverage of mural renin-expressing cells (17,31,32,47,63); however, their function is unclear. Adult renin-expressing cells are restricted to the juxtaglomerular apparatus and play a vital role in ion homeostasis by secreting activated renin enzyme via cytoplasmic granules (17,31,36,63). Upon physiological challenge by RAS inhibition or low Na ϩ , prearteriolar vascular smooth muscle cells (VSMC) reestablish their embryonic re...

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“…Kidneys were harvested after 72 hours and processed for whole-mount X-gal staining followed by postfixation, embedding, sectioning, and immunostaining as previously described. 50 …”

Section: Measurement Of Endothelial Proliferationmentioning

confidence: 99%

Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular Development

Li²,

Göthert

et al. 2015

JASN

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The close relationship between endothelial and hematopoietic precursors during early development of the vascular system suggested the possibility of a common yet elusive precursor for both cell types. Whether similar or related progenitors for endothelial and hematopoietic cells are present during organogenesis is unclear. Using inducible transgenic mice that specifically label endothelial and hematopoietic precursors, we performed fate-tracing studies combined with colony-forming assays and crosstransplantation studies. We identified a progenitor, marked by the expression of helix-loop-helix transcription factor stem cell leukemia (SCL/Tal1). During organogenesis of the kidney, SCL/Tal1 + progenitors gave rise to endothelium and blood precursors with multipotential colony-forming capacity. Furthermore, appropriate morphogenesis of the kidney vasculature, including glomerular capillary development, arterial mural cell coating, and lymphatic vessel development, required sphingosine 1-phosphate (S1P) signaling via the G protein-coupled S1P receptor 1 in these progenitors. Overall, these results show that SCL/Tal1 + progenitors with hemogenic capacity originate and differentiate within the early embryonic kidney by hemovasculogenesis (the concomitant formation of blood and vessels) and underscore the importance of the S1P pathway in vascular development.

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Renin Cells Are Precursors for Multiple Cell Types that Switch to the Renin Phenotype When Homeostasis Is Threatened

Cited by 237 publications

References 22 publications

Deletion of von Hippel–Lindau Protein Converts Renin-Producing Cells into Erythropoietin-Producing Cells

Deletion of von Hippel–Lindau Protein Converts Renin-Producing Cells into Erythropoietin-Producing Cells

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular Development

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