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Kidney International. Supplement Sep 1998The mammalian nephron has a unique structure called juxtaglomerular apparatus (JGA); the primary function of the JGA includes tubuloglomerular feedback. Why is such a... (Review)
Review
The mammalian nephron has a unique structure called juxtaglomerular apparatus (JGA); the primary function of the JGA includes tubuloglomerular feedback. Why is such a structure necessary? Analyses of available data strongly suggest that JGA has evolved to provide a fine tuning of the autoregulation of glomerular hemodynamics and high glomerular filtration rate in the face of very limited salt intake of our terrestrial environment, a function essential to allow a wide range of fluid and electrolyte intake with stable milieu interieur. Salt intake in excess is unique only to recent human cultures: salt intake is ordinarily less than 1 to 2 g per 60 kg of body weight in wildlife, including paleolithic humans. Any mutation or alteration of JGA function leading to renal salt conservation or maladaptive to high salt intake will not manifest in a low salt intake and thus would have been beneficial or inconsequential for survival in a natural environment, respectively. Thus, the mutation or alteration will be carried to subsequent generations. However, such altered function will result in essential hypertension or a maladaptation of JGA to high salt intake, which is a unique behavior of human civilizations of recent centuries. The kidney has not adapted to high salt intake through our evolution.
Topics: Feedback; Humans; Hypertension, Renal; Kidney Glomerulus; Kidney Tubules; Sodium, Dietary
PubMed: 9736257
DOI: 10.1046/j.1523-1755.1998.06714.x -
IScience Nov 2022Succinate dehydrogenase (SDH)-deficient renal cell carcinoma represents a rare subtype of hereditary kidney cancer. Clinical diagnosis can be challenging and there is...
Succinate dehydrogenase (SDH)-deficient renal cell carcinoma represents a rare subtype of hereditary kidney cancer. Clinical diagnosis can be challenging and there is little evidence to guide systemic therapeutic options. We performed genomic profiling of a cohort of tumors through the analysis of whole genomes, transcriptomes, as well as flow cytometry and immunohistochemistry in order to gain a deeper understanding of their molecular biology. We find neutral evolution after early tumor activation with a lack of secondary driver events. We show that these tumors have epithelial derivation, possibly from the macula densa, a specialized paracrine cell of the renal juxtaglomerular apparatus. They subsequently develop into immune excluded tumors. We provide transcriptomic and protein expression evidence of a highly specific tumor marker, PAPPA2. These translational findings have implications for the diagnosis and treatment for this rare tumor subtype.
PubMed: 36345344
DOI: 10.1016/j.isci.2022.105389 -
Journal of Biomedical Optics Feb 2014The structural and functional heterogeneity of the kidney ensures a diversity of response in health and disease. Multiphoton microscopy has improved our understanding of... (Review)
Review
The structural and functional heterogeneity of the kidney ensures a diversity of response in health and disease. Multiphoton microscopy has improved our understanding of kidney physiology and pathophysiology by enabling the visualization of the living kidney in comparison with the static view of previous technologies. The use of multiphoton microscopy with rodent models in conjunction with endogenous fluorescence and exogenous infused dyes permits the measurement of renal processes, such as glomerular permeability, juxtaglomerular apparatus function, tubulointerstitial function, tubulovascular interactions, vascular flow rate, and the intrarenal renin-angiotensin-aldosterone system. Subcellular processes, including mitochondrial dynamics, reactive oxygen species production, cytosolic ion concentrations, and death processes apoptosis and necrosis, can also be measured by multiphoton microscopy. This has allowed valuable insight into the pathophysiology of diabetic nephropathy, renal ischemia-reperfusion injury, hypertensive nephropathy, as well as inflammatory responses of the kidney. The current review presents an overview of multiphoton microscopy with a focus on techniques for imaging the kidney and gives examples of instances where multiphoton microscopy has been utilized to study renal pathophysiology in the living kidney. With continued advancements in the field of biological optics and increased adoption in experimental nephrology, multiphoton microscopy will undoubtedly continue to create new paradigms in kidney disease.
Topics: Animals; Kidney; Kidney Diseases; Mice; Microscopy, Fluorescence, Multiphoton; Rats
PubMed: 24525825
DOI: 10.1117/1.JBO.19.2.020901 -
The Tohoku Journal of Experimental... Jan 1992In each nephron of the mammalian kidney, the tubule returns to the hilus of the parent glomerulus, forming the juxtaglomerular apparatus (JGA). The JGA displays a unique... (Review)
Review
In each nephron of the mammalian kidney, the tubule returns to the hilus of the parent glomerulus, forming the juxtaglomerular apparatus (JGA). The JGA displays a unique arrangement of afferent and efferent arterioles, interstitial cells and macula densa (a specialized plaque of tubular epithelial cells). Because of this intimate anatomical relationship, it has long been suggested that the macula densa may somehow sense changes in the composition of the tubular fluid and control both the glomerular filtration rate and renin release. Despite extensive investigation, attempts to obtain direct evidence of this have been hindered by the anatomical complexity of the JGA. However, recent technical developments now permit direct assessment of the role of the macula densa in the control of both renin release and glomerular hemodynamics. These developments include microdissection/perfusion of the afferent arteriole, the macula densa or both, as well as a sensitive renin assay which permits measurement of renin release from a single JGA. Observations resulting from such developments are discussed in this article.
Topics: Animals; Humans; Kidney Glomerulus; Renal Circulation; Renin
PubMed: 1412445
DOI: 10.1620/tjem.166.27 -
Autopsy & Case Reports 2022Juxtaglomerular cell tumor is a benign, renin-secreting neoplasm. The tumor arises from the juxtaglomerular apparatus cells of the kidney. Because the tumor is...
Juxtaglomerular cell tumor is a benign, renin-secreting neoplasm. The tumor arises from the juxtaglomerular apparatus cells of the kidney. Because the tumor is hormonally active, patients usually suffer from hypokalemia, hyperaldosteronism, and hypertension. Herein, we describe a case of a 19-year-old Asian female with a somewhat unusual presentation. A 19-year-old Asian female presented with upper extremity weakness, numbness, and tingling. On physical examination, the only notable finding was hypertension. Extensive workup revealed elevated aldosterone level and plasma renin activity. CT scan of the abdomen revealed a 2.2 cm mass in the lower pole of the left kidney. The mass was resected by partial nephrectomy. On microscopic evaluation, the tumor had glomoid appearance with sheets of uniform, round to polygonal cells with clear to eosinophilic cytoplasm. Immunohistochemical stains showed the tumor cells to be positive for CD117, CD34 and CD10 and negative for ER, PR, CK7, PAX-8, pan-cytokeratin, EMA, S100, Melan-A, HMB45, SMA and CAIX. Diagnosis of Juxtaglomerular cell tumor was rendered. This case highlights the importance of a regular physical exam and a high index of suspicion in patients presenting with unusual complaints.
PubMed: 36312876
DOI: 10.4322/acr.2021.406 -
Kidney International. Supplement Sep 1998Prostaglandin E2 is the major cyclooxygenase product of arachidonic acid metabolism produced along the nephron. This autacoid interacts with four distinct,... (Review)
Review
Prostaglandin E2 is the major cyclooxygenase product of arachidonic acid metabolism produced along the nephron. This autacoid interacts with four distinct, G-protein-coupled E-prostanoid receptors designated EP1-EP4. The intrarenal distribution of each receptor has been mapped and the consequences of receptor activation examined. EP3 receptor mRNA is expressed highly in the medullary thick ascending limb (mTAL) and collecting duct (CD). EP3 receptor activation inhibits cAMP generation via Gi, thus inhibiting vasopressin-stimulated water reabsorption in the CD. EP3 receptor activation also may contribute to PGE2-mediated inhibition of NaCl absorption in the mTAL. The EP1 receptor is coupled to increased cell [Ca2+]. EP1 mRNA expression is restricted to the CD, and receptor activation inhibits Na+ absorption. PGE2 also increases cAMP generation in the cortical thick ascending limb and CD; this may be due to EP4 receptor activation. EP4 mRNA is readily detected in the CD with little detectable EP2 expression. The EP4 receptor appears to be expressed both on luminal and basolateral membranes. EP4 receptor activation also may contribute to the regulation of renin release by the juxtaglomerular apparatus. The consequences of renal EP-receptor activation for salt and water balance may be determined by the relative renal expression of each of these receptors.
Topics: Animals; Kidney; Nephrons; Receptors, Prostaglandin E
PubMed: 9736261
DOI: 10.1046/j.1523-1755.1998.06718.x -
American Journal of Physiology. Renal... Dec 2021Macula densa (MD) cells, a chief sensory cell type in the nephron, are endowed with unique microanatomic features including a high density of protein synthetic...
Macula densa (MD) cells, a chief sensory cell type in the nephron, are endowed with unique microanatomic features including a high density of protein synthetic organelles and secretory vesicles in basal cell processes ("maculapodia") that suggest a so far unknown high rate of MD protein synthesis. This study aimed to explore the rate and regulation of MD protein synthesis and their effects on glomerular function using novel transgenic mouse models, newly established fluorescence cell biology techniques, and intravital microscopy. Sox2-tdTomato kidney tissue sections and an -propargyl puromycin incorporation-based fluorescence imaging assay showed that MD cells have the highest level of protein synthesis within the kidney cortex followed by intercalated cells and podocytes. Genetic gain of function of mammalian target of rapamycin (mTOR) signaling specifically in MD cells (in MD-mTOR mice) or their physiological activation by low-salt diet resulted in further significant increases in the synthesis of MD proteins. Specifically, these included both classic and recently identified MD-specific proteins such as cyclooxygenase 2, microsomal prostaglandin E synthase 1, and pappalysin 2. Intravital imaging of the kidney using multiphoton microscopy showed significant increases in afferent and efferent arteriole and glomerular capillary diameters and blood flow in MD-mTOR mice coupled with an elevated glomerular filtration rate. The presently identified high rate of MD protein synthesis that is regulated by mTOR signaling is a novel component of the physiological activation and glomerular hemodynamic regulatory functions of MD cells that remains to be fully characterized. This study discovered the high rate of protein synthesis in macula densa (MD) cells by applying direct imaging techniques with single cell resolution. Physiological activation and mammalian target of rapamycin signaling played important regulatory roles in this process. This new feature is a novel component of the tubuloglomerular cross talk and glomerular hemodynamic regulatory functions of MD cells. Future work is needed to elucidate the nature and (patho)physiological role of the specific proteins synthesized by MD cells.
Topics: Animals; Autocrine Communication; Diet, Sodium-Restricted; Glomerular Filtration Rate; Green Fluorescent Proteins; Humans; Intravital Microscopy; Juxtaglomerular Apparatus; Luminescent Proteins; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Fluorescence, Multiphoton; Nitric Oxide Synthase Type I; Paracrine Communication; Protein Biosynthesis; Renin; Signal Transduction; Sodium, Dietary; TOR Serine-Threonine Kinases; Tuberous Sclerosis Complex 2 Protein; Red Fluorescent Protein; Mice
PubMed: 34693742
DOI: 10.1152/ajprenal.00222.2021 -
American Journal of Physiology. Renal... Nov 2012
Topics: Animals; Connexins; Endothelium, Vascular; Juxtaglomerular Apparatus; Kidney Tubules; Paracrine Communication; Gap Junction alpha-5 Protein
PubMed: 22952283
DOI: 10.1152/ajprenal.00494.2012 -
Journal of Clinical Hypertension... Aug 2017Juxtaglomerular cell tumor (JGCT) is a rare tumor, with approximately 100 cases reported in the literature. The authors respectively studied the clinical data of 11...
Juxtaglomerular cell tumor (JGCT) is a rare tumor, with approximately 100 cases reported in the literature. The authors respectively studied the clinical data of 11 patients diagnosed with JGCT in Peking Union Medical College Hospital from 2004 to 2014, and investigated the immunohistochemical profiles in 10 tumors. Nine of the 11 patients were diagnosed before the age of 40 years. Hypertension was present in all patients, while hypokalemia occurred in seven of 11 patients. Computed tomography detected JGCTs with a sensitivity of 100%. Immunoreactivities for CD34 and vascular endothelial growth factor were observed in most tumor specimens, suggesting that JGCTs express a variety of vessel-related immunohistochemical markers, although JGCTs are considered a tumor without abundant blood supply. Nuclear accumulation of cyclin D1 was common in JGCTs. Results from immunohistochemistry were negative for BRAF, HER2, and TFE3, suggesting that BRAF, HER2, and TFE3 genes might not play a part in tumorigenesis in JGCTs.
Topics: Adolescent; Adult; Aged; Antigens, CD34; Child; Comorbidity; Epidermal Growth Factor; Female; Humans; Hypertension; Hypokalemia; Juxtaglomerular Apparatus; Kidney Neoplasms; Male; Middle Aged; Retrospective Studies; Tomography, X-Ray Computed; Young Adult
PubMed: 28317244
DOI: 10.1111/jch.12997 -
General and Comparative Endocrinology Sep 2020Renin or a renin-like enzyme evolved in ancestral vertebrates and is conserved along the vertebrate phylogeny. The ontogenic development of renin, however, is not well...
Renin or a renin-like enzyme evolved in ancestral vertebrates and is conserved along the vertebrate phylogeny. The ontogenic development of renin, however, is not well understood in nonmammalian vertebrates. We aimed to determine the expression patterns and relative abundance of renin mRNA in pre- and postnatal chickens (Gallus gallus, White Leghorn breed). Embryonic day 13 (E13) embryos show renal tubules, undifferentiated mesenchymal structures, and a small number of developing glomeruli. Maturing glomeruli are seen in post-hatch day 4 (D4) and day 30 (D30) kidneys, indicating that nephrogenic activity still exists in kidneys of 4-week-old chickens. In E13 embryos, renin mRNA measured by quantitative polymerase chain reaction in the adrenal glands is equivalent to the expression in the kidneys, whereas in post-hatch D4 and D30 maturing chicks, renal renin expressions increased 2-fold and 11-fold, respectively. In contrast, relative renin expression in the adrenals became lower than in the kidneys. Furthermore, renin expression is clearly visible by in situ hybridization in the juxtaglomerular (JG) area in D4 and D30 chicks, but not in E13 embryos. The results suggest that in chickens, renin evolved in both renal and extrarenal organs at an early stage of ontogeny and, with maturation, became localized to the JG area. Clear JG structures are not morphologically detectable in E13 embryos, but are visible in 30-day-old chicks, supporting this concept.
Topics: Animals; Chick Embryo; Chickens; Gene Expression Regulation; Juxtaglomerular Apparatus; Organogenesis; RNA, Messenger; Renin; Renin-Angiotensin System
PubMed: 32561435
DOI: 10.1016/j.ygcen.2020.113533