(Verbatim from the application): Renin cell progenitors originate in situ within the differentiating kidney rather than from extrarenal vessels. During early mouse embryonic development (E12), these cells are present in the undifferentiated metanephric mesenchyme, before vascularization of the kidney has occurred and before the hemodynamic functions of renin are needed. Later in fetal, life, renin cells are found along intrarenal arteries, in glomeruli, and among interstitial cells. With maturation, renin cells become restricted to the classical adult juxtaglomerular (JG) localization. If an adult animal is subjected to manipulations that threaten homeostasis, there is an increase in the number of renin-expressing cells along preglomerular arteries, interstitium and glomeruli resembling the embryonic pattern. It is likely that the ability of adult kidney cells to re-express renin depends on the lineage of the cell involved. It has been suggested that JO cells originate from smooth muscle cells. However, our preliminary data suggest just the opposite. The fate of renin cells remains to be studied. Similarly; the timing of appearance of these cells in branching points of differentiating renal arterioles suggests a role for JG cell precursors in the development of the kidney vasculature. Finally, some strains of mice have more than one renin gene: Ren 1 and Ren 2. The role of each of these genes in lineage determination and morphogenesis is unknown. Using in vivo fate mapping, chimeric mice, and cell ablation techniques we propose to adress the following hypotheses: (1) in addition to JG cells, renin cell precursors give rise to (rather than originate from) renal arteriolar smooth muscle cells, pericytes and mesangial cells, (2) renin cell descendants are the only kidney cells capable of metaplastic transformation to the renin phenotype, (3) expression of renin is necessary for JO cell and arteriolar differentiation and Ren I and Ren 2 regulate the differentiation of distinct and separate renin cells; (4) JG cells per se (independent of renin) are necessary for nephrovascular development. The studies should generate fundamental new knowledge on JG cell differentiation and function and open new avenues for the understanding, prevention and treatment of hypertension and kidney diseases.
| Oka, Masafumi; Medrano, Silvia; Sequeira-L?pez, Maria Luisa S et al. (2017) Chronic Stimulation of Renin Cells Leads to Vascular Pathology. Hypertension 70:119-128 |
| Gomez, R Ariel (2017) Fate of Renin Cells During Development and Disease. Hypertension 69:387-395 |
| Hu, Yan; Li, Minghong; Göthert, Joachim R et al. (2016) Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular Development. J Am Soc Nephrol 27:1984-95 |
| Lu, Ko-Ting; Keen, Henry L; Weatherford, Eric T et al. (2016) Estrogen Receptor ? Is Required for Maintaining Baseline Renin Expression. Hypertension 67:992-9 |
| Gomez, R Ariel; Belyea, Brian; Medrano, Silvia et al. (2014) Fate and plasticity of renin precursors in development and disease. Pediatr Nephrol 29:721-6 |
| Medrano, Silvia; Monteagudo, Maria C; Sequeira-Lopez, Maria Luisa S et al. (2012) Two microRNAs, miR-330 and miR-125b-5p, mark the juxtaglomerular cell and balance its smooth muscle phenotype. Am J Physiol Renal Physiol 302:F29-37 |
| Xu, Di; Borges, Giulianna R; Davis, Deborah R et al. (2011) Neuron- or glial-specific ablation of secreted renin does not affect renal renin, baseline arterial pressure, or metabolism. Physiol Genomics 43:286-94 |
| Desch, Michael; Schreiber, Andrea; Schweda, Frank et al. (2010) Increased renin production in mice with deletion of peroxisome proliferator-activated receptor-gamma in juxtaglomerular cells. Hypertension 55:660-6 |
| Chen, Limeng; Kim, Soo Mi; Eisner, Christoph et al. (2010) Stimulation of renin secretion by angiotensin II blockade is Gsalpha-dependent. J Am Soc Nephrol 21:986-92 |
| Sequeira-Lopez, Maria Luisa S; Weatherford, Eric T; Borges, Giulianna R et al. (2010) The microRNA-processing enzyme dicer maintains juxtaglomerular cells. J Am Soc Nephrol 21:460-7 |
Showing the most recent 10 out of 18 publications
