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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 -
Giornale Italiano Di Cardiologia (2006) Apr 2021The liver is not the exclusive site of glucose production in humans in the post-absorption state. Experimental data showed that the kidney is able of carrying out... (Review)
Review
The liver is not the exclusive site of glucose production in humans in the post-absorption state. Experimental data showed that the kidney is able of carrying out gluconeogenesis. Renal glucose production accounts for 20% of systemic glucose production. Evidence indicates that the kidney is able to reabsorb glucose from the glomerular filtrate through the sodium-glucose co-transporters (SGLT) 1 and 2 placed under the Bowman's capsule, in the thick portion of the proximal convoluted tubule, preserving this essential energy substrate for the organism. The maximal renal glucose reabsorption capacity (TmG), as well as the threshold for the spillover of glucose in the urine, are higher in diabetics than normal subjects and contribute to the hyperglycemic state in the absence of glycosuria. The administration of SGLT2 inhibitors in diabetics improves the excretion of sodium and glucose, reducing the threshold of glycosuria and TmG. This also restores the sodium concentration in the filtrate that reaches the macula densa (juxtaglomerular apparatus), which signals the appropriate perfusion of the kidney, defusing the secretion of renin and the activation of the neurohormonal axis that leads to the production of angiotensin II.Large clinical trials conducted with SGLT2 inhibitors in subjects with type 2 diabetes mellitus have demonstrated the great ability of this new class of drugs to achieve cardiac and renal benefits. All studies have shown SGLT2 inhibitors reduce the risk of hospitalizations for heart failure and the progression of kidney damage. A part of the favorable mechanisms is mediated by the natriuretic effect that is associated with the glycosuric effect, which reduces the activation of the renin-angiotensin-aldosterone system together with glomerular hyperfiltration.The aim of this review is to expand the knowledge among general cardiologists on the role of SGLT2 and SGLT1 in renal glucose homeostasis in healthy and diabetic subjects in the light of a potent class of drugs counteracting heart failure.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glucose; Heart Failure; Humans; Hypoglycemic Agents; Kidney; Sodium; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33783448
DOI: 10.1714/3574.35574 -
American Journal of Physiology. Renal... Mar 2021
Topics: Juxtaglomerular Apparatus; Kidney Tubules; Sodium Chloride, Dietary
PubMed: 33586498
DOI: 10.1152/ajprenal.00051.2021 -
Genes Feb 2021Spindle cell hemangioma is a benign vascular tumor typically occurring in the dermis or subcutis of distal extremities as red-brown lesions that can grow in both size...
Spindle cell hemangioma is a benign vascular tumor typically occurring in the dermis or subcutis of distal extremities as red-brown lesions that can grow in both size and number over time. They can be very painful and potentially disabling. A family history of cancer or previous history may be relevant and must be taken into consideration. Juxtaglomerular cell tumor (reninoma) is an extremely rare cause of secondary hypertension diagnosed mostly among adolescents and young adults. Excessive renin secretion results in secondary hyperaldosteronism. Subsequent hypokalemia and metabolic alkalosis, together with high blood pressure, are clues for clinical diagnosis. Histological examination of the excised tumor leads to a definitive diagnosis. Reninoma is found in subcapsular localization, in most cases as a solitary mass, in imaging studies of kidneys. Exceptionally, it can be located in another part of a kidney. Both spindle cell hemangioma and reninoma are extremely rare tumors in children and adolescents. Herein, the authors present a case report of a patient with hereditary BRCA1 interacting protein C-terminal helicase 1 (BRIP1) mutation, spindle cell hemangioma, and secondary hypertension caused by atypically localized reninoma.
Topics: Fanconi Anemia Complementation Group Proteins; Genetic Predisposition to Disease; Germ-Line Mutation; Hemangioma; Humans; Juxtaglomerular Apparatus; Kidney; RNA Helicases
PubMed: 33546375
DOI: 10.3390/genes12020220 -
American Journal of Physiology. Renal... Mar 2021Although macula densa (MD) cells are chief regulatory cells in the nephron with unique microanatomical features, they have been difficult to study in full detail due to...
Although macula densa (MD) cells are chief regulatory cells in the nephron with unique microanatomical features, they have been difficult to study in full detail due to their inaccessibility and limitations in earlier microscopy techniques. The present study used a new mouse model with a comprehensive imaging approach to visualize so far unexplored microanatomical features of MD cells, their regulation, and functional relevance. MD-GFP mice with conditional and partial induction of green fluorescent protein (GFP) expression, which specifically and intensely illuminated only single MD cells, were used with fluorescence microscopy of fixed tissue and live MD cells in vitro and in vivo with complementary electron microscopy of the rat, rabbit, and human kidney. An elaborate network of major and minor cell processes, here named maculapodia, were found at the cell base, projecting toward other MD cells and the glomerular vascular pole. The extent of maculapodia showed upregulation by low dietary salt intake and the female sex. Time-lapse imaging of maculapodia revealed highly dynamic features including rapid outgrowth and an extensive vesicular transport system. Electron microscopy of rat, rabbit, and human kidneys and three-dimensional volume reconstruction in optically cleared whole-mount MD-GFP mouse kidneys further confirmed the presence and projections of maculapodia into the extraglomerular mesangium and afferent and efferent arterioles. The newly identified dynamic and secretory features of MD cells suggest the presence of novel functional and molecular pathways of cell-to-cell communication in the juxtaglomerular apparatus between MD cells and between MD and other target cells. This study illuminated a physiologically regulated dense network of basal cell major and minor processes (maculapodia) in macula densa (MD) cells. The newly identified dynamic and secretory features of these microanatomical structures suggest the presence of novel functional and molecular pathways of cell-to-cell communication in the juxtaglomerular apparatus between MD and other target cells. Detailed characterization of the function and molecular details of MD cell intercellular communications and their role in physiology and disease warrant further studies.
Topics: Animals; Cell Communication; Epithelial Cells; Glomerular Mesangium; Juxtaglomerular Apparatus; Kidney Glomerulus; Kidney Tubules; Mice; Rabbits; Rats
PubMed: 33491562
DOI: 10.1152/ajprenal.00546.2020 -
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 -
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 -
Anatomy & Cell Biology Dec 2020Camillo Golgi was an extraordinary scientist whose contributions in the domain of neuroanatomy proved to be critical for emergence of neuroscience as a sovereign... (Review)
Review
Camillo Golgi was an extraordinary scientist whose contributions in the domain of neuroanatomy proved to be critical for emergence of neuroscience as a sovereign scientific discipline. Golgi's invention of the () was a watershed event as it allowed remarkable visualization of the organizational pattern of elements of nervous system among complex puzzle of close knit interconnections. Till this time thin filamentary extensions of neural cells (axon and dendrites) could not be visualized with available staining techniques because of their slender and transparent nature. However invention of and its subsequent application demystified the basic architecture of brain tissue which was now visible to the scholars in all its complexity in microscopic studies. Golgi is also credited with the discovery of two types of sensory receptors in muscle tendons: Golgi tendon organ and Golgi-Mazzoni corpuscles. Golgi was the first to be successful in staining myelin component of axon, which he used to discover the myelin annular apparatus. He identified the complete life cycle of Plasmodium (malarial parasite) in human erythrocytes. His research on histological details of human kidney highlighted the existence of juxtaglomerular apparatus. Later on Spanish scientist Santiago Ramón y Cajal, based on the use of Golgi's Staining (Black Reaction) documented the morphologic details of nervous system in a more refined manner, which eventually led to the emergence of . In recognition of their exemplary contributions in neuroscience Golgi and Cajal were jointly awarded the Nobel Prize for Physiology or Medicine in 1906.
PubMed: 33012727
DOI: 10.5115/acb.20.196 -
Medicine Sep 2020Based on existing literature, the juxtaglomerular cell tumor (JGCT) is a rare renal tumor, typically present with hypertension and hypokalemia. Nonfunctioning JGCT,...
INTRODUCTION
Based on existing literature, the juxtaglomerular cell tumor (JGCT) is a rare renal tumor, typically present with hypertension and hypokalemia. Nonfunctioning JGCT, without hypertension or hypokalemia, is extremely rare.
PATIENT CONCERNS
Herein, we report a case of nonfunctioning JGCT mimicking renal cell carcinoma. The 29-year-old woman with an unremarkable past medical history presented with a left renal tumor without hypertension or hypokalemia.
DIAGNOSIS
Both CT and 18F-FDG-PET/CT suggested a malignancy, possibly renal cell carcinoma.
INTERVENTIONS
The tumor was then removed completely via robotic assistant laparoscopic partial nephrectomy; and pathology result was JGCT. Since the patient had no hypertension or hypokalemia, a nonfunctional JGCT was diagnosed.
OUTCOMES
The patient recovered uneventfully, and was in good health in 6-months' follow-up period.
CONCLUSION
Preoperative identification of JGCT is very difficult due to the lack of specific clinical manifestations. This case teaches us that for young patients with renal tumors whose CT enhancement is not obvious at the early phase, JGCT should be considered as a differential diagnosis. Radical nephrectomy should be avoided for JGCT in consideration of its relatively good prognosis.
Topics: Adult; Aftercare; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Fluorodeoxyglucose F18; Humans; Juxtaglomerular Apparatus; Kidney Neoplasms; Laparoscopy; Neoplasms; Nephrectomy; Positron Emission Tomography Computed Tomography; Robotic Surgical Procedures; Treatment Outcome
PubMed: 32899070
DOI: 10.1097/MD.0000000000022057 -
Frontiers in Physiology 2020The juxtaglomerular apparatus (JGA) is an essential structure in the regulation of renal function. The JGA embodies two major functions: tubuloglomerular feedback (TGF)...
The juxtaglomerular apparatus (JGA) is an essential structure in the regulation of renal function. The JGA embodies two major functions: tubuloglomerular feedback (TGF) and renin secretion. TGF is one of the mechanisms mediating renal autoregulation. It is initiated by an increase in tubular NaCl concentration at the macula densa cells. This induces a local afferent arteriolar vasoconstriction and a conducted response that can be measured several 100 μm upstream from the juxtaglomerular segment. This spread of the vasomotor response into the surrounding vasculature likely plays a key role in renal autoregulation, and it requires the presence of gap junctions, intercellular pores based on connexin (Cx) proteins. Several Cx isoforms are expressed in the JGA and in the arteriolar wall. Disruption of this communication pathway is associated with reduced TGF, dysregulation of renin secretion, and hypertension. We examine if the absence of Cx40 or Cx45, expressed in the endothelial and vascular smooth muscle cells respectively, attenuates afferent arteriolar local and conducted vasoconstriction. Afferent arterioles from wildtype and Cx-deficient mice (Cx40 and Cx45) were studied using the isolated perfused juxtamedullary nephron preparation. Vasoconstriction was induced electrical pulse stimulation at the glomerular entrance. Inner afferent arteriolar diameter was measured locally and upstream to evaluate conducted vasoconstriction. Electrical stimulation induced local vasoconstriction in all groups. The local vasoconstriction was significantly smaller when Cx40 was absent. The vasoconstriction decreased in magnitude with increasing distance from the stimulation site. In both Cx40 and Cx45 deficient mice, the vasoconstriction conducted a shorter distance along the vessel compared to wild-type mice. In Cx40 deficient arterioles, this may be caused by a smaller local vasoconstriction. Collectively, these findings imply that Cx40 and Cx45 are central for normal vascular reactivity and, therefore, likely play a key role in TGF-induced regulation of afferent arteriolar resistance.
PubMed: 32848881
DOI: 10.3389/fphys.2020.00961