The Experts below are selected from a list of 918 Experts worldwide ranked by ideXlab platform
William H Beierwaltes - One of the best experts on this subject based on the ideXlab platform.
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salt restriction leads to activation of adult renal mesenchymal stromal Cell like Cells via prostaglandin e2 and e prostanoid receptor 4
Hypertension, 2015Co-Authors: Yanqiang Yang, Jose A Gomez, Marcela Herrera, Romelia Perezmarco, Peter Repenning, Zhiping Zhang, Alan Payne, Richard E Pratt, Beverly H Koller, William H BeierwaltesAbstract:Despite the importance of Juxtaglomerular Cell recruitment in the pathophysiology of cardiovascular diseases, the mechanisms that underlie renin production under conditions of chronic stimulation remain elusive. We have previously shown that CD44+ mesenchymal-like Cells (CD44+ Cells) exist in the adult kidney. Under chronic sodium deprivation, these Cells are recruited to the Juxtaglomerular area and differentiate to new renin-expressing Cells. Given the proximity of macula densa to the Juxtaglomerular area and the importance of macula densa released prostanoids in renin synthesis and release, we hypothesized that chronic sodium deprivation induces macula densa release of prostanoids, stimulating renal CD44+ Cell activation and differentiation. CD44+ Cells were isolated from adult kidneys and cocultured with the macula densa Cell line, MMDD1, in normal or low-sodium medium. Low sodium stimulated prostaglandin E2 production by MMDD1 and induced migration of CD44+ Cells. These effects were inhibited by addition of a cyclooxygenase 2 inhibitor (NS398) or an E-prostanoid receptor 4 antagonist (AH23848) to MMDD1 or CD44+ Cells, respectively. Addition of prostaglandin E2 to CD44+ Cells increased Cell migration and induced renin expression. In vivo activation of renal CD44+ Cells during Juxtaglomerular recruitment was attenuated in wild-type mice subjected to salt restriction in the presence of cyclooxygenase 2 inhibitor rofecoxib. Similar results were observed in E-prostanoid receptor 4 knockout mice subjected to salt restriction. These results show that the prostaglandin E2/E-prostanoid receptor 4 pathway plays a key role in the activation of renal CD44+ mesenchymal stromal Cell-like Cells during conditions of Juxtaglomerular recruitment; highlighting the importance of this pathway as a key regulatory mechanism of Juxtaglomerular recruitment.
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Juxtaglomerular Cell casr stimulation decreases renin release via activation of the plc ip3 pathway and the ryanodine receptor
American Journal of Physiology-renal Physiology, 2013Co-Authors: Cecilia M Ortizcapisano, William H Beierwaltes, Mahendranath Reddy, Mariela Mendez, Jeffrey L GarvinAbstract:The calcium-sensing receptor (CaSR) is a G-coupled protein expressed in renal Juxtaglomerular (JG) Cells. Its activation stimulates calcium-mediated decreases in cAMP content and inhibits renin rel...
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parathyroid hormone stimulates Juxtaglomerular Cell camp accumulation without stimulating renin release
American Journal of Physiology-renal Physiology, 2012Co-Authors: Douglas K. Atchison, William H Beierwaltes, Pamela Harding, Edward L. Peterson, Cecilia M OrtizcapisanoAbstract:Parathyroid hormone (PTH) is positively coupled to the generation of cAMP via its actions on the PTH1R and PTH2R receptors. Renin secretion from Juxtaglomerular (JG) Cells is stimulated by elevated...
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without stimulating renin
2012Co-Authors: Douglas K. Atchison, William H Beierwaltes, Pamela Harding, Cecilia M. Ortiz-capisano, Edward L. Peterson, Harding PAbstract:hormone stimulates Juxtaglomerular Cell cAMP accumulatio
Armin Kurtz - One of the best experts on this subject based on the ideXlab platform.
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phenotypic dissection of the mouse ren1d knockout by complementation with human renin
Journal of Biological Chemistry, 2017Co-Authors: Charlotte Buckley, Matthew G. F. Sharp, Stewart Fleming, Janos Petipeterdi, Robert Nelson, Linda J Mullins, Christopher J Kenyon, Sabrina Semprini, Dominik Steppan, Armin KurtzAbstract:Normal renin synthesis and secretion is important for the maintenance of Juxtaglomerular apparatus architecture. Mice lacking a functional Ren1d gene are devoid of renal Juxtaglomerular Cell granules and exhibit an altered macula densa morphology. Due to the species-specificity of renin activity, transgenic mice are ideal models for experimentally investigating and manipulating expression patterns of the human renin gene in a native Cellular environment without confounding renin-angiotensin system interactions. A 55-kb transgene encompassing the human renin locus was crossed onto the mouse Ren1d-null background, restoring granulation in Juxtaglomerular Cells. Correct processing of human renin in dense core granules was confirmed by immunogold labeling. After stimulation of the renin-angiotensin system, Juxtaglomerular Cells contained rhomboid protogranules with paracrystalline contents, dilated rough endoplasmic reticulum, and electron-lucent granular structures. However, complementation of Ren1d-/- mice with human renin was unable to rescue the abnormality seen in macula densa structure. The Juxtaglomerular apparatus was still able to respond to tubuloglomerular feedback in isolated perfused Juxtaglomerular apparatus preparations, although minor differences in glomerular tuft contractility and macula densa Cell calcium handling were observed. This study reveals that the human renin protein is able to complement the mouse Ren1d-/- non-granulated defect and suggests that granulopoiesis requires a structural motif that is conserved between the mouse Ren1d and human renin proteins. It also suggests that the altered macula densa phenotype is related to the activity of the renin-1d enzyme in a local Juxtaglomerular renin-angiotensin system.
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Substitution of connexin40 with connexin45 prevents hyperreninemia and attenuates hypertension
Kidney international, 2008Co-Authors: Frank Schweda, Lisa Kurtz, C. De Wit, Ulrike Janssen-bienhold, Armin Kurtz, Charlotte WagnerAbstract:Connexins (Cxs) are a family of transmembrane proteins that form gap junctions with unique and redundant biophysical functions. Juxtaglomerular Cells express Cx40, which is crucial to the control of renin secretion by blood pressure and angiotensin II, and mice that lack Cx40 have high plasma renin and hypertension. To examine whether normal Juxtaglomerular Cell function depends on the unique properties of Cx40, we measured renin release in mice where the coding sequence for Cx40 was replaced by that for Cx45, using the knock-in method. We first found that the knock-in strategy indeed resulted in expression of Cx45 but not Cx40 in the Juxtaglomerular Cells of these mice. The plasma renin concentration of the knock-in mice was similar to that in wild-type mice. The high blood pressure of the Cx40 knockout mice was significantly reduced when Cx45 was knocked into the locus but remained mildly elevated compared to wild-type mice. Blockade of angiotensin II formation by enalapril increased the plasma renin concentration in wild-type and the Cx45 knock-in mice but not in the Cx40 knockout mice. Infusion of angiotensin II into isolated perfused kidneys results in decreased renin release, a phenomenon that was attenuated in the Cx40 knockout mice. However, in the Cx45 knock-in mice, angiotensin II suppressed renin release similar to its effect in wild type mice. Unilateral renal artery stenosis increased the plasma renin concentration and blood pressure in both the wild-type and the Cx45 knock-in mice but not in the Cx40 knockout mice. Since Cx40 can be replaced by Cx45, a connexin with a significantly lower conductivity, we suggest that the regulation of renin release is not dependent on the unique electrical properties of these channel proteins.
Jose A Gomez - One of the best experts on this subject based on the ideXlab platform.
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abstract 137 sox6 regulates renin expression during Juxtaglomerular Cell expansion
Hypertension, 2017Co-Authors: Jason D Foss, Liang Xiao, Kandi Horton, Mohammad Saleem, Conrad P Hodgkinson, David G Harrison, Jose A GomezAbstract:Introduction: Hypertension, a common condition that affects 33% of the US population, is a major risk factor for heart disease and stroke. Treatments for hypertension are limited and there is a cri...
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salt restriction leads to activation of adult renal mesenchymal stromal Cell like Cells via prostaglandin e2 and e prostanoid receptor 4
Hypertension, 2015Co-Authors: Yanqiang Yang, Jose A Gomez, Marcela Herrera, Romelia Perezmarco, Peter Repenning, Zhiping Zhang, Alan Payne, Richard E Pratt, Beverly H Koller, William H BeierwaltesAbstract:Despite the importance of Juxtaglomerular Cell recruitment in the pathophysiology of cardiovascular diseases, the mechanisms that underlie renin production under conditions of chronic stimulation remain elusive. We have previously shown that CD44+ mesenchymal-like Cells (CD44+ Cells) exist in the adult kidney. Under chronic sodium deprivation, these Cells are recruited to the Juxtaglomerular area and differentiate to new renin-expressing Cells. Given the proximity of macula densa to the Juxtaglomerular area and the importance of macula densa released prostanoids in renin synthesis and release, we hypothesized that chronic sodium deprivation induces macula densa release of prostanoids, stimulating renal CD44+ Cell activation and differentiation. CD44+ Cells were isolated from adult kidneys and cocultured with the macula densa Cell line, MMDD1, in normal or low-sodium medium. Low sodium stimulated prostaglandin E2 production by MMDD1 and induced migration of CD44+ Cells. These effects were inhibited by addition of a cyclooxygenase 2 inhibitor (NS398) or an E-prostanoid receptor 4 antagonist (AH23848) to MMDD1 or CD44+ Cells, respectively. Addition of prostaglandin E2 to CD44+ Cells increased Cell migration and induced renin expression. In vivo activation of renal CD44+ Cells during Juxtaglomerular recruitment was attenuated in wild-type mice subjected to salt restriction in the presence of cyclooxygenase 2 inhibitor rofecoxib. Similar results were observed in E-prostanoid receptor 4 knockout mice subjected to salt restriction. These results show that the prostaglandin E2/E-prostanoid receptor 4 pathway plays a key role in the activation of renal CD44+ mesenchymal stromal Cell-like Cells during conditions of Juxtaglomerular recruitment; highlighting the importance of this pathway as a key regulatory mechanism of Juxtaglomerular recruitment.
Stewart Fleming - One of the best experts on this subject based on the ideXlab platform.
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phenotypic dissection of the mouse ren1d knockout by complementation with human renin
Journal of Biological Chemistry, 2017Co-Authors: Charlotte Buckley, Matthew G. F. Sharp, Stewart Fleming, Janos Petipeterdi, Robert Nelson, Linda J Mullins, Christopher J Kenyon, Sabrina Semprini, Dominik Steppan, Armin KurtzAbstract:Normal renin synthesis and secretion is important for the maintenance of Juxtaglomerular apparatus architecture. Mice lacking a functional Ren1d gene are devoid of renal Juxtaglomerular Cell granules and exhibit an altered macula densa morphology. Due to the species-specificity of renin activity, transgenic mice are ideal models for experimentally investigating and manipulating expression patterns of the human renin gene in a native Cellular environment without confounding renin-angiotensin system interactions. A 55-kb transgene encompassing the human renin locus was crossed onto the mouse Ren1d-null background, restoring granulation in Juxtaglomerular Cells. Correct processing of human renin in dense core granules was confirmed by immunogold labeling. After stimulation of the renin-angiotensin system, Juxtaglomerular Cells contained rhomboid protogranules with paracrystalline contents, dilated rough endoplasmic reticulum, and electron-lucent granular structures. However, complementation of Ren1d-/- mice with human renin was unable to rescue the abnormality seen in macula densa structure. The Juxtaglomerular apparatus was still able to respond to tubuloglomerular feedback in isolated perfused Juxtaglomerular apparatus preparations, although minor differences in glomerular tuft contractility and macula densa Cell calcium handling were observed. This study reveals that the human renin protein is able to complement the mouse Ren1d-/- non-granulated defect and suggests that granulopoiesis requires a structural motif that is conserved between the mouse Ren1d and human renin proteins. It also suggests that the altered macula densa phenotype is related to the activity of the renin-1d enzyme in a local Juxtaglomerular renin-angiotensin system.
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Renin-1 Is Essential for Normal Renal Juxtaglomerular Cell Granulation and Macula Densa Morphology
Journal of Biological Chemistry, 1997Co-Authors: Allan F. Clark, Matthew G. F. Sharp, Steven D. Morley, Stewart Fleming, Jörg Peters, John J. MullinsAbstract:Abstract The secretion of renin from granules stored in renal Juxtaglomerular Cells plays a key role in blood pressure homeostasis. The synthesis and release of renin and the extent of granulation is regulated by several mechanisms including signaling from the macula densa, neuronal input, and blood pressure. Through the use of a gene-targeting vector containing homology arms generated using the polymerase chain reaction, we have inactivated theRen-1 d gene, one of two mouse genes encoding renin, and report that lack of renin-1d results in altered morphology of the macula densa of the kidney distal tubule and complete absence of Juxtaglomerular Cell granulation. Furthermore,Ren-1 d−/− mice exhibit sexually dimorphic hypotension. The altered growth morphology of the macula densa in Ren-1d -null mice should provide a tool for the investigation of the JG Cell-macula densa signaling. Furthermore, the current data indicate that expression of theRen-1 d gene is a prerequisite for the formation of storage granules, even though the related protein renin-2 is present in these mice, suggesting that renin-1d and renin-2 are secreted by distinct pathways in vivo.
Matthew G. F. Sharp - One of the best experts on this subject based on the ideXlab platform.
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phenotypic dissection of the mouse ren1d knockout by complementation with human renin
Journal of Biological Chemistry, 2017Co-Authors: Charlotte Buckley, Matthew G. F. Sharp, Stewart Fleming, Janos Petipeterdi, Robert Nelson, Linda J Mullins, Christopher J Kenyon, Sabrina Semprini, Dominik Steppan, Armin KurtzAbstract:Normal renin synthesis and secretion is important for the maintenance of Juxtaglomerular apparatus architecture. Mice lacking a functional Ren1d gene are devoid of renal Juxtaglomerular Cell granules and exhibit an altered macula densa morphology. Due to the species-specificity of renin activity, transgenic mice are ideal models for experimentally investigating and manipulating expression patterns of the human renin gene in a native Cellular environment without confounding renin-angiotensin system interactions. A 55-kb transgene encompassing the human renin locus was crossed onto the mouse Ren1d-null background, restoring granulation in Juxtaglomerular Cells. Correct processing of human renin in dense core granules was confirmed by immunogold labeling. After stimulation of the renin-angiotensin system, Juxtaglomerular Cells contained rhomboid protogranules with paracrystalline contents, dilated rough endoplasmic reticulum, and electron-lucent granular structures. However, complementation of Ren1d-/- mice with human renin was unable to rescue the abnormality seen in macula densa structure. The Juxtaglomerular apparatus was still able to respond to tubuloglomerular feedback in isolated perfused Juxtaglomerular apparatus preparations, although minor differences in glomerular tuft contractility and macula densa Cell calcium handling were observed. This study reveals that the human renin protein is able to complement the mouse Ren1d-/- non-granulated defect and suggests that granulopoiesis requires a structural motif that is conserved between the mouse Ren1d and human renin proteins. It also suggests that the altered macula densa phenotype is related to the activity of the renin-1d enzyme in a local Juxtaglomerular renin-angiotensin system.
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Renin-1 Is Essential for Normal Renal Juxtaglomerular Cell Granulation and Macula Densa Morphology
Journal of Biological Chemistry, 1997Co-Authors: Allan F. Clark, Matthew G. F. Sharp, Steven D. Morley, Stewart Fleming, Jörg Peters, John J. MullinsAbstract:Abstract The secretion of renin from granules stored in renal Juxtaglomerular Cells plays a key role in blood pressure homeostasis. The synthesis and release of renin and the extent of granulation is regulated by several mechanisms including signaling from the macula densa, neuronal input, and blood pressure. Through the use of a gene-targeting vector containing homology arms generated using the polymerase chain reaction, we have inactivated theRen-1 d gene, one of two mouse genes encoding renin, and report that lack of renin-1d results in altered morphology of the macula densa of the kidney distal tubule and complete absence of Juxtaglomerular Cell granulation. Furthermore,Ren-1 d−/− mice exhibit sexually dimorphic hypotension. The altered growth morphology of the macula densa in Ren-1d -null mice should provide a tool for the investigation of the JG Cell-macula densa signaling. Furthermore, the current data indicate that expression of theRen-1 d gene is a prerequisite for the formation of storage granules, even though the related protein renin-2 is present in these mice, suggesting that renin-1d and renin-2 are secreted by distinct pathways in vivo.
