Human kidney pericytes produce renin

Stefanska, Ania; Kenyon, Christopher J.; Christian, Helen C.; Buckley, Charlotte; Shaw, Isaac; Mullins, John J.; Péault, Bruno

doi:10.1016/j.kint.2016.07.035

Cited by 52 publications

(45 citation statements)

References 64 publications

(79 reference statements)

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“…17 Importantly, pericytes in the human kidney were recently reported to produce renin. 18 Hypoxia transforms renin-producing cells into erythropoietin-producing cells, 19 and erythropoietin-expressing cells are assumed to be derived from capillary pericytes. 20 Finally, following severe mesangial injury, renin-positive precursor cells moved into intraglomerular sites and differentiated into (renin-negative), PDGFRβ-expressing mesangial cells.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Human Reninomas as an Approach to Understanding Juxtaglomerular Cell Biology

Martini

Lacombe

et al. 2017

Hypertension

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Renin, a key component in the regulation of blood pressure in mammals, is produced by the rare and highly specialized juxtaglomerular (JG) cells of the kidney. Chronic stimulation of renin release results in a recruitment of new JG cells by the apparent conversion of adjacent smooth muscle cells along the afferent arterioles. Because JG cells rapidly de-differentiate when removed from the kidney, their developmental origin and the mechanism that explains their phenotypic plasticity remain unclear. To overcome this limitation we have performed RNA expression analysis on four human renin-producing tumors. The most highly expressed genes that were common between the reninomas were subsequently used for in situ hybridization in kidneys of 5-day old mice, adult mice and mice treated with captopril. From the top 100 genes, 10 encoding for ligands were selected for further analysis. Medium of HEK293 cells transfected with the mouse cDNA encoding these ligands was applied to (pro)renin-synthesizing As4.1 cells. Among the ligands, only platelet-derived growth factor B (PDGFB) reduced the medium and cellular (pro)renin levels, as well as As4.1 renin gene expression. Additionally, PDGFB-exposed As4.1 cells displayed a more elongated and aligned shape with no alteration in viability. This was accompanied by a downregulated expression of α-smooth muscle actin, and an upregulated expression of interleukin-6, suggesting a phenotypic shift from myo-endocrine to inflammatory. Our results add 36 new genes to the list that characterize renin-producing cells and reveal a novel role for PDGFB as a regulator of renin-synthesizing cells.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Human Reninomas as an Approach to Understanding Juxtaglomerular Cell Biology

Martini

Lacombe

et al. 2017

Hypertension

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“…Importantly, perivascular progenitor cells have an essentially universal ability to form mineral deposits in vitro. This is even observed among pericytes isolated form visceral depots . The extent to which the ability to form in vivo bone is a universal feature of pericytes derived from any tissue is controversial.…”

Section: Tissue Sources Of Osteogenic Pericytesmentioning

confidence: 99%

“…This is even observed among pericytes isolated form visceral depots. 4,13,43 The extent to which the ability to form in vivo bone is a universal feature of pericytes derived from any tissue is controversial. Among subcutaneous implants, skeletal muscle-derived pericytes showed no evidence of bone formation.…”

Section: Tissue Sources Of Osteogenic Pericytesmentioning

confidence: 99%

“…As we have showed, renin-producing cells in afferent juxtaglomerular arterioles are also specialized pericytes. 43,55 Conversely, other potentials of pericytes exhibit an amazing lack of organ specificity; for instance, while the hematopoietic stem cell niche in the bone marrow is well recognized to be mostly composed of pericytes, the same cells purified from skeletal muscle and adipose tissue exhibit a dramatic ability to sustain hematopoietic stem cells in vitro. 56,57…”

Section: Tissue-specific Properties Of Pericytesmentioning

confidence: 99%

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Perivascular Mesenchymal Progenitors for Bone Regeneration

James

Péault

2019

Journal Orthopaedic Research

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Mesenchymal progenitor cells reside in all assayed vascularized tissues, and are broadly conceptualized to participate in homeostasis/renewal and repair. The application of mesenchymal progenitor cells has been studied for diverse orthopaedic conditions related to skeletal degeneration, regeneration, and tissue fabrication. One common niche for mesenchymal progenitors is the perivascular space, and in both mouse and human tissues, perivascular progenitor cells have been isolated and characterized. Of these “perivascular stem cells” or PSC, pericytes are the most commonly studied cells. Multiple studies have demonstrated the regenerative properties of PSC when applied to bone, including direct osteochondral differentiation, paracrine‐induced osteogenesis and vasculogenesis, and immunomodulatory functions. The confluence of these effects have resulted in efficacious bone regeneration across several preclinical models. Yet, key topics of research in perivascular progenitors highlight our lack of knowledge regarding these cell populations. These ongoing areas of study include cellular diversity within the perivascular niche, tissue‐specific properties of PSC, and factors that influence PSC‐mediated regenerative potential. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1221–1228, 2019.

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“…Renin-secreting cells of the kidney, which are typically located in a juxtaglomerular position at the entrance of afferent arterioles into their glomeruli, are the key regulators of the renin-angiotensin-aldosterone system. From their origin, they are pericyte-related cells [9] which descend from the FoxD1positive stroma progenitor compartment of the kidney [2]. It is well established that the number of renin-secreting cells can increase by hyperplasia and also by reversible metaplastic transformation of "silent" renin-producing cells into active renin producers and vice versa [4].…”

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confidence: 99%

How can juxtaglomerular renin-producing cells support the integrity of glomerular endothelial cells?

Kurtz

2019

Pflugers Arch - Eur J Physiol

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Over the last years, findings have been accumulated to indicate that renin-producing cells and their "silent" precursors show a striking degree of plasticity not only to regulate renin. Renin-secreting cells of the kidney, which are typically located in a juxtaglomerular position at the entrance of afferent arterioles into their glomeruli, are the key regulators of the renin-angiotensin-aldosterone system. From their origin, they are pericyte-related cells [9] which descend from the FoxD1positive stroma progenitor compartment of the kidney [2]. It is well established that the number of renin-secreting cells can increase by hyperplasia and also by reversible metaplastic transformation of "silent" renin-producing cells into active renin producers and vice versa [4]. The common genomic signature of "silent" and of active renin-producing cells has recently been unraveled [6]. A key step for renin expression is activation of the cyclic AMP signaling cascade [4].Synthesis and secretion also serve other functions. Thus, it has been shown that genetic activation of the hypoxia signaling pathway in renin cells suppresses renin expression and induces erythropoietin expression [3]. Moreover, renin cells or their "silent" precursors have been found to serve glomerular function, for instance by repopulating the mesangium after mesangial cell injury [8]. Further evidence in this context has been reported that renin cells might also act as precursors for podocytes after podocyte damage [1]. Although renin cells cannot repopulate damaged glomerular endothelial cells [7], they appear to exert a protective effect on endothelial cells. The article by Steglich and coworkers entitled "Renin cells with defective Gsα/cAMP-signaling contribute to renal endothelial damage" as published in this issue of Pflügers Archiv now confirms and extends previous findings that renin cells have also influence on the integrity of the glomerular endothelium [5]. The authors report that continuous disruption of cAMP signaling by renin cell-specific deletion of the Gsα protein downregulated renin expression as expected, but in addition also led to endothelial damage of glomerular capillaries as indicated by the change of morphological and genetic markers. In reverse, this finding could indicate that intact cAMP signaling in juxtaglomerular cells is required for normal glomerular endothelial function. The authors present data that indicate that a loss of renin cells and the concomitant decrease in renin production induced by the expression of diphtheria toxin in renin cells per se exert no apparent detrimental effect on endothelial cells. They also found that deletion of Gsα protein in renin cells did not destroy the cells but instead caused a phenotype switch to a renin-negative and fibroblast-like cell. The authors suggest that the new profibrotic cell phenotype directly or indirectly causes endothelial damage. Notably, genetic induction of the hypoxia signaling pathway causes a similar profibrotic phenotype shift of renin cells as does deletion of Gsα ...

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Human kidney pericytes produce renin

Cited by 52 publications

References 64 publications

Transcriptome Analysis of Human Reninomas as an Approach to Understanding Juxtaglomerular Cell Biology

Transcriptome Analysis of Human Reninomas as an Approach to Understanding Juxtaglomerular Cell Biology

Perivascular Mesenchymal Progenitors for Bone Regeneration

How can juxtaglomerular renin-producing cells support the integrity of glomerular endothelial cells?

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