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High Blood Pressure & Cardiovascular... Sep 2017Renin is the first and rate-limiting step of the renin-angiotensin system. The exclusive source of renin in the circulation are the juxtaglomerular cells of the kidney,... (Review)
Review
Renin is the first and rate-limiting step of the renin-angiotensin system. The exclusive source of renin in the circulation are the juxtaglomerular cells of the kidney, which line the afferent arterioles at the entrance of the glomeruli. Normally, renin production by these cells suffices to maintain homeostasis. However, under chronic stimulation of renin release, for instance during a low-salt diet or antihypertensive therapy, cells that previously expressed renin during congenital life re-convert to a renin-producing cell phenotype, a phenomenon which is known as "recruitment". How exactly such differentiation occurs remains to be clarified. This review critically discusses the phenotypic plasticity of renin cells, connecting them not only to the classical concept of blood pressure regulation, but also to more complex contexts such as development and growth processes, cell repair mechanisms and tissue regeneration.
Topics: Animals; Calcium Signaling; Cardiovascular Diseases; Cell Plasticity; Cyclic AMP; Cyclic GMP; Embryonic Stem Cells; Epigenesis, Genetic; Humans; Juxtaglomerular Apparatus; Kidney Diseases; Phenotype; Regeneration; Renin-Angiotensin System; Second Messenger Systems
PubMed: 28527017
DOI: 10.1007/s40292-017-0212-5 -
Nature Communications Sep 2023Reninomas are exceedingly rare renin-secreting kidney tumours that derive from juxtaglomerular cells, specialised smooth muscle cells that reside at the vascular inlet...
Reninomas are exceedingly rare renin-secreting kidney tumours that derive from juxtaglomerular cells, specialised smooth muscle cells that reside at the vascular inlet of glomeruli. They are the central component of the juxtaglomerular apparatus which controls systemic blood pressure through the secretion of renin. We assess somatic changes in reninoma and find structural variants that generate canonical activating rearrangements of, NOTCH1 whilst removing its negative regulator, NRARP. Accordingly, in single reninoma nuclei we observe excessive renin and NOTCH1 signalling mRNAs, with a concomitant non-excess of NRARP expression. Re-analysis of previously published reninoma bulk transcriptomes further corroborates our observation of dysregulated Notch pathway signalling in reninoma. Our findings reveal NOTCH1 rearrangements in reninoma, therapeutically targetable through existing NOTCH1 inhibitors, and indicate that unscheduled Notch signalling may be a disease-defining feature of reninoma.
Topics: Humans; Renin; Kidney Neoplasms; Juxtaglomerular Apparatus; Kidney Glomerulus; Signal Transduction; Receptor, Notch1
PubMed: 37749094
DOI: 10.1038/s41467-023-41118-8 -
European Endocrinology Oct 2020Therapeutic advances have revolutionised cancer treatment over the last two decades, but despite improved survival and outcomes, adverse effects to anticancer therapy... (Review)
Review
Therapeutic advances have revolutionised cancer treatment over the last two decades, but despite improved survival and outcomes, adverse effects to anticancer therapy such as dyselectrolytaemias do occur and need to be managed appropriately. This review explores essential aspects of sodium homeostasis in cancer with a focus on alterations arising from anticancer medications. Sodium and water balance are tightly regulated by close interplay of stimuli arising from hypothalamic osmoreceptors, arterial and atrial baroreceptors and the renal juxtaglomerular apparatus. This delicate balance can be disrupted by cancer itself, as well as the medications used to treat it. Some of the conventional chemotherapeutics, such as alkylating agents and platinum-based drugs, can cause hyponatraemia and, on rare occasions, hypernatraemia. Other conventional agents such as vinca alkaloids, as well as newer targeted cancer therapies including small molecule inhibitors and monoclonal antibodies, can cause hyponatraemia, usually as a result of inappropriate antidiuretic hormone secretion. Hyponatraemia can also sometimes occur secondarily to drug-induced hypocortisolism or salt-wasting syndromes. Another atypical but distinct mechanism for hyponatraemia is via pituitary dysfunction induced by immune checkpoint inhibitors. Hypernatraemia is uncommon and occasionally ensues as a result of drug-induced nephrogenic diabetes insipidus. Identification of the aetiology and appropriate management of these conditions, in addition to averting treatment-related problems, can be lifesaving in critical situations.
PubMed: 33117443
DOI: 10.17925/EE.2020.16.2.122 -
Circulation Research Apr 2021Renin cells are essential for survival perfected throughout evolution to ensure normal development and defend the organism against a variety of homeostatic threats.... (Review)
Review
Renin cells are essential for survival perfected throughout evolution to ensure normal development and defend the organism against a variety of homeostatic threats. During embryonic and early postnatal life, they are progenitors that participate in the morphogenesis of the renal arterial tree. In adult life, they are capable of regenerating injured glomeruli, control blood pressure, fluid-electrolyte balance, tissue perfusion, and in turn, the delivery of oxygen and nutrients to cells. Throughout life, renin cell descendants retain the plasticity or memory to regain the renin phenotype when homeostasis is threatened. To perform all of these functions and maintain well-being, renin cells must regulate their identity and fate. Here, we review the major mechanisms that control the differentiation and fate of renin cells, the chromatin events that control the memory of the renin phenotype, and the major pathways that determine their plasticity. We also examine how chronic stimulation of renin cells alters their fate leading to the development of a severe and concentric hypertrophy of the intrarenal arteries and arterioles. Lastly, we provide examples of additional changes in renin cell fate that contribute to equally severe kidney disorders.
Topics: Animals; Arterioles; Blood Pressure; Cell Communication; Cell Differentiation; Cell Plasticity; Chromatin; Chromatin Assembly and Disassembly; Connexins; Homeostasis; Humans; Hypertension; Integrins; Juxtaglomerular Apparatus; Kidney; Kidney Glomerulus; Mice; MicroRNAs; Phenotype; Regeneration; Renal Artery; Renin; Renin-Angiotensin System; Stem Cells; Water-Electrolyte Balance
PubMed: 33793334
DOI: 10.1161/CIRCRESAHA.121.318064 -
Pflugers Archiv : European Journal of... Aug 2022The protease renin, the key enzyme of the renin-angiotensin-aldosterone system, is mainly produced and secreted by juxtaglomerular cells in the kidney, which are located... (Review)
Review
The protease renin, the key enzyme of the renin-angiotensin-aldosterone system, is mainly produced and secreted by juxtaglomerular cells in the kidney, which are located in the walls of the afferent arterioles at their entrance into the glomeruli. When the body's demand for renin rises, the renin production capacity of the kidneys commonly increases by induction of renin expression in vascular smooth muscle cells and in extraglomerular mesangial cells. These cells undergo a reversible metaplastic cellular transformation in order to produce renin. Juxtaglomerular cells of the renin lineage have also been described to migrate into the glomerulus and differentiate into podocytes, epithelial cells or mesangial cells to restore damaged cells in states of glomerular disease. More recently, it could be shown that renin cells can also undergo an endocrine and metaplastic switch to erythropoietin-producing cells. This review aims to describe the high degree of plasticity of renin-producing cells of the kidneys and to analyze the underlying mechanisms.
Topics: Cell Differentiation; Juxtaglomerular Apparatus; Kidney; Kidney Glomerulus; Mesangial Cells; Myocytes, Smooth Muscle; Podocytes; Renin; Renin-Angiotensin System
PubMed: 35511367
DOI: 10.1007/s00424-022-02694-8 -
International Journal of Molecular... Oct 2022In the essential homeostatic role of kidney, two intrarenal mechanisms are prominent: the glomerulotubular balance driving the process of Na and water reabsorption in... (Review)
Review
In the essential homeostatic role of kidney, two intrarenal mechanisms are prominent: the glomerulotubular balance driving the process of Na and water reabsorption in the proximal tubule, and the tubuloglomerular feedback which senses the Na concentration in the filtrate by the juxtaglomerular apparatus to provide negative feedback on the glomerular filtration rate. In essence, the two mechanisms regulate renal oxygen consumption. The renal hyperfiltration driven by increased glomerular filtration pressure and by glucose diuresis can affect renal O consumption that unleashes detrimental sympathetic activation. The sodium-glucose co-transporters inhibitors (SGLTi) can rebalance the reabsorption of Na coupled with glucose and can restore renal O demand, diminishing neuroendocrine activation. Large randomized controlled studies performed in diabetic subjects, in heart failure, and in populations with chronic kidney disease with and without diabetes, concordantly address effective action on heart failure exacerbations and renal adverse outcomes.
Topics: Diabetes Mellitus; Diabetic Nephropathies; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 36233288
DOI: 10.3390/ijms231911987 -
Hypertension (Dallas, Tex. : 1979) Mar 2017Although renin cells are crucial for blood pressure homeostasis, little is known about their nature. We now know that renin cells are precursors that appear early and in... (Review)
Review
Although renin cells are crucial for blood pressure homeostasis, little is known about their nature. We now know that renin cells are precursors that appear early and in multiple tissues during embryonic development. They participate in morphogenetic events, vascular development and injury, tissue repair and regeneration. When confronted to a homeostatic threat, renin cell descendants have the capability to switch the renin gene on or off. This poorly understood switch or molecular memory enables the organism to maintain constancy of the internal milieu and tissue perfussion. Here, we discuss briefly the major events that govern the acquisition and maintenace of renin cell identity and how manipulations that alter the fate of renin cells can lead to serious disease. We also advance the concept that renin cells are at the center of an ancestral sytem of defense linking the endocrine, the immune and repair responses of the organism.
Topics: Animals; Humans; Juxtaglomerular Apparatus; Kidney; Renin; Renin-Angiotensin System
PubMed: 28137982
DOI: 10.1161/HYPERTENSIONAHA.116.08316 -
International Journal of Molecular... Nov 2020Our study analyzed the expression pattern of different connexins (Cxs) and renin positive cells in the juxtaglomerular apparatus (JGA) of developing, postnatal healthy...
Our study analyzed the expression pattern of different connexins (Cxs) and renin positive cells in the juxtaglomerular apparatus (JGA) of developing, postnatal healthy human kidneys and in nephrotic syndrome of the Finnish type (CNF), by using double immunofluorescence, electron microscopy and statistical measuring. The JGA contained several cell types connected by Cxs, and consisting of macula densa, extraglomerular mesangium (EM) and juxtaglomerular cells (JC), which release renin involved in renin-angiotensin- aldosteron system (RAS) of arterial blood pressure control. During JGA development, strong Cx40 expression gradually decreased, while expression of Cx37, Cx43 and Cx45 increased, postnatally showing more equalized expression patterning. In parallel, initially dispersed renin cells localized to JGA, and greatly increased expression in postnatal kidneys. In CNF kidneys, increased levels of Cx43, Cx37 and Cx45 co-localized with accumulations of renin cells in JGA. Additionally, they reappeared in extraglomerular mesangial cells, indicating association between return to embryonic Cxs patterning and pathologically changed kidney tissue. Based on the described Cxs and renin expression patterning, we suggest involvement of Cx40 primarily in the formation of JGA in developing kidneys, while Cx37, Cx43 and Cx45 might participate in JGA signal transfer important for postnatal maintenance of kidney function and blood pressure control.
Topics: Child; Connexin 43; Connexins; Female; Fetus; Gap Junctions; Humans; Infant; Juxtaglomerular Apparatus; Kidney; Kidney Tubules; Male; Myocytes, Smooth Muscle; Nephrotic Syndrome; Renin; Renin-Angiotensin System; Signal Transduction; Gap Junction alpha-5 Protein; Gap Junction alpha-4 Protein
PubMed: 33172216
DOI: 10.3390/ijms21218349