Maturation of TonEBP expression in developing rat kidney

2004 ◽  
Vol 287 (5) ◽  
pp. F878-F885 ◽  
Author(s):  
Ki-Hwan Han ◽  
Seung Kyoon Woo ◽  
Wan-Young Kim ◽  
Soo-Hyun Park ◽  
Jung-Ho Cha ◽  
...  
Keyword(s):  
Target Genes ◽  
Kidney Development ◽  
Rat Kidney ◽  
Renal Medulla ◽  
Organic Osmolytes ◽  
Vasa Recta ◽  
Enhancer Binding Protein ◽  
Genes Encoding ◽  
Urinary Concentrating Ability

Tonicity-responsive enhancer binding protein (TonEBP) is a transcriptional activator of the Rel family. In the renal medulla, TonEBP stimulates genes encoding proteins involved in cellular accumulation of organic osmolytes, the vasopressin-regulated urea transporters (UT-A), and heat shock protein 70. To understand the role of TonEBP in the development of urinary concentrating ability, TonEBP expression during rat kidney development was investigated. In embryonic kidneys, TonEBP immunoreactivity was detected 16 days postcoitus in the cytoplasm of the endothelial cells surrounding the medullary collecting ducts (MCD). By 20 days, TonEBP was detected in most tubular profiles in the medulla, including the loop of Henle and MCD, and interstitial cells. The intensity of TonEBP immunoreactivity was much higher in the vasa recta than the tubules. In addition, immunoreactivity was localized predominantly to the cytoplasm. On postnatal day 1, two major changes were observed. TonEBP immunoreactivity shifted to the nucleus, and the intensity of TonEBP immunoreactivity of the tubules increased dramatically. These changes were associated with an increase in TonEBP and sodium- myo-inositol cotransporter mRNA abundance. Thereafter, TonEBP expression in tubular profiles increased moderately. The adult pattern of TonEBP expression was established at postnatal day 21 coincident with full maturation of the renal medulla. Thus expression of TonEBP in developing kidneys occurred predominantly in the medulla and preceded expression of its target genes, including UT-A. These data suggest that TonEBP contributes to the development of urine-concentrating ability.

scholarly journals TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress: organic osmolyte-dependent and -independent pathways

2011 ◽  
Vol 300 (3) ◽  
pp. F707-F715 ◽  
Author(s):  
Sang Do Lee ◽  
Soo Youn Choi ◽  
Sun Woo Lim ◽  
S. Todd Lamitina ◽  
Steffan N. Ho ◽  
...  
Keyword(s):  
Rna Interference ◽  
Target Genes ◽  
Binding Protein ◽  
Renal Medulla ◽  
Organic Osmolytes ◽  
Hypertonic Stress ◽  
Osmolyte Accumulation ◽  
Organic Osmolyte ◽  
Enhancer Binding Protein ◽  
Cellular Pathways

TonEBP (tonicity-responsive enhancer binding protein) is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that the genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Of over 100 potentially new TonEBP-regulated genes, we selected seven for further analyses and found that their expressions were all dependent on TonEBP. RNA interference experiments showed that some of these genes, asporin, insulin-like growth factor-binding protein-5 and -7, and an extracellular lysophospholipase D, plus heat shock protein 70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation.

Influence of the renal medullary circulation on the control of sodium excretion

1993 ◽  
Vol 265 (5) ◽  
pp. R963-R973 ◽  
Author(s):  
R. J. Roman ◽  
A. P. Zou
Keyword(s):  
Blood Flow ◽  
Renal Perfusion ◽  
Sodium Reabsorption ◽  
Doppler Flowmetry ◽  
Medullary Blood Flow ◽  
Tubular Sodium Reabsorption ◽  
Vasa Recta ◽  
Urinary Concentrating Ability ◽  
Reliable Methods

Although the role of the renal medullary circulation in the control of urinary concentrating ability is well established, its potential influence on tubular sodium reabsorption is not generally recognized. Nearly 30 years ago, changes in the intrarenal distribution of blood flow were first proposed to contribute to the natriuretic response to volume expansion. However, the lack of reliable methods for studying medullary blood flow limited progress in this area. The recent development of laser-Doppler flowmetry and videomicroscopic techniques for the study of the vasa recta circulation has renewed interest in the role of medullary hemodynamics in the control of sodium reabsorption. Results of these studies indicate that changes in renal medullary hemodynamics alter renal interstitial pressure and the medullary solute gradient and play an important role in the natriuretic response to elevations in renal perfusion pressure, intravenous infusion of saline, and changes in tubular sodium reabsorption produced by vasoactive compounds. What is emerging from these studies is the view that changes in renal medullary hemodynamics represent an important but misunderstood and long-ignored factor in the control of tubular sodium reabsorption.

Renal medullary blood flow: its measurement and physiology

1986 ◽  
Vol 64 (7) ◽  
pp. 873-880 ◽  
Author(s):  
W. A. Cupples
Keyword(s):  
Blood Flow ◽  
Renal Medulla ◽  
Vascular Bundles ◽  
Medullary Blood Flow ◽  
Vasa Recta ◽  
Countercurrent Exchange ◽  
Renal Medullary Blood Flow ◽  
Urinary Concentrating Ability ◽  
Velocity Tracking ◽  
Uptake Method

The vasculature of the mammalian renal medulla is complex, having neither discrete input nor output. There is also efficient countercurrent exchange between ascending and descending vasa recta in the vascular bundles. These considerations have hampered measurement of medullary blood flow since they impose pronounced constraints on methods used to assess flow. Three main strategies have been used: (i) indicator extraction; (ii) erythrocyte velocity tracking; and (iii) indicator dilution. These are discussed with respect to their assumptions, requirements, and limitations. There is a consensus that medullary blood flow is autoregulated, albeit over a narrower pressure range than is total renal blood flow. When normalized to gram tissue weight, medullary blood flow in the dog is similar to that in the rat, on the order of 1 to 1.5 mL∙min−1∙g−1. This is considerably greater than estimated by the radioiodinated albumin uptake method which has severe conceptual and practical problems. From both theoretical and experimental evidence it ssems that urinary concentrating ability is considerably less sensitive to changes in medullary blood flow than is often assumed.

Analysis of microvascular water and solute exchanges in the renal medulla

1984 ◽  
Vol 247 (2) ◽  
pp. F303-F315 ◽  
Author(s):  
T. L. Pallone ◽  
T. I. Morgenthaler ◽  
W. M. Deen
Keyword(s):  
Renal Medulla ◽  
Blood Flow Rate ◽  
Reflection Coefficients ◽  
Hydraulic Permeability ◽  
Mass Balances ◽  
Flow Rates ◽  
Corticomedullary Junction ◽  
Vasa Recta ◽  
Capillary Plexus

A theoretical model has been developed to simulate solute and water transport in the medullary microcirculation of the normal hydropenic rat. The model is formulated in terms of a countercurrent vascular unit consisting of one descending (DVR) and several ascending vasa recta (AVR) extending from the corticomedullary junction to the tip of the papilla. Steady-state mass balances relate gradients in NaCl, urea, and plasma protein concentrations and variations in the flow rates of plasma and red blood cells to permeability properties of the vasa recta and erythrocytes. In contrast to previous models, transmural volume fluxes are assumed to be present in both DVR and AVR. Available micropuncture measurements suggesting net volume removal from DVR within the inner medulla are found to be consistent with NaCl reflection coefficients in DVR between 0.10 and 0.80. The hydraulic permeability in the DVR is estimated to be greater than 0.18 X 10(-6) cm X s-1 X mmHg-1. Based on currently available data, reliable bounds cannot yet be placed on the hydraulic permeability of the AVR. The vascular unit is predicted to accomplish substantial net removal of NaCl and water from the inner medullary interstitium but relatively little removal of urea. Red cells leaving the inner medulla in the AVR are found to be slightly dehydrated. It is calculated that at a given blood flow rate, the lower the initial medullary hematocrit, the more effective the vascular unit is at removing water. Several unresolved issues are discussed, including the role of the capillary plexus that joins DVR with AVR. To the extent that the volume uptake observed in the exposed papilla in structures beyond the DVR occurs in the capillary plexus and not in the AVR, estimated values of AVR hydraulic permeability are reduced, as is predicted overall volume uptake by the vascular unit in the inner medulla.

Autoregulation of blood flow in renal medulla of the rat: no role for angiotensin II

1988 ◽  
Vol 66 (6) ◽  
pp. 833-836 ◽  
Author(s):  
W. A. Cupples ◽  
D. J. Marsh
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Lower Limit ◽  
Enzyme Inhibitor ◽  
Renal Medulla ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitor ◽  
Upper Limit ◽  
Vasa Recta

Autoregulation of blood flow was assessed by a dual-slit technique in descending and ascending vasa recta of the exposed renal papillae of antidiuretic rats. There was complete autoregulation of blood flow in descending vasa recta. The lower limit of autoregulation was approximately 85 mmHg (1 mmHg = 133.3 Pa) and the upper limit was greater then 160 mmHg. Auto-regulation in ascending vasa recta was also good. To test the role of angiotensin II in this autoregulation, the converting enzyme inhibitor captopril was infused. Captopril had no effect on autoregulation of blood flow in either descending or ascending vasa recta. We conclude that blood flow in vasa recta of renal medulla is efficiently autoregulated and that this autoregulation is independent of angiotensin II

Developmental expression of aquaporin 1 in the rat renal vasculature

1999 ◽  
Vol 276 (4) ◽  
pp. F498-F509 ◽  
Author(s):  
Jin Kim ◽  
Wan-Young Kim ◽  
Ki-Hwan Han ◽  
Mark A. Knepper ◽  
Søren Nielsen ◽  
...  
Keyword(s):  
Kidney Development ◽  
Rat Kidney ◽  
Water Channel ◽  
Developmental Expression ◽  
Renal Tubules ◽  
Renal Vasculature ◽  
Aquaporin 1 ◽  
Vasa Recta ◽  
Adult Kidney ◽  
Developing Rat

Aquaporin 1 (AQP-1) is a water channel protein that is constitutively expressed in renal proximal tubule and descending thin limb cells as well as in endothelial cells of the descending vasa recta. Studies in the developing rat kidney have demonstrated that AQP-1 is expressed in renal tubules before birth. However, nothing is known about the expression of AQP-1 in the renal vasculature during kidney development. The purpose of this study was to establish the distribution of AQP-1 in the renal vasculature of the developing rat kidney and follow the differentiation of the vascular system during kidney development. Kidneys from 16-, 17-, 18-, and 20-day-old fetuses and 1-, 4-, 7-, 14-, 21-, and 28-day-old pups were preserved and processed for immunohistochemical studies using a preembedding immunoperoxidase procedure. AQP-1 immunoreactivity was detected using affinity-purified rabbit polyclonal antibodies to AQP-1. AQP-1 was expressed throughout the arterial portion of the renal vasculature of the fetal and neonatal kidney from gestational age 17 days to 1 wk after birth. AQP-1 immunoreactivity gradually disappeared from the renal vasculature between 1 and 2 wk of age and remained only in the descending vasa recta. In contrast, AQP-1 immunoreactivity was not observed in lymphatic vessels until 3 wk of age and persisted in the adult kidney. AQP-1 was also expressed in a population of interstitial cells in the terminal part of the renal papilla at 3 wk of age as well as in the adult kidney. The transient expression of AQP-1 in the arterial portion of the renal vasculature in the developing rat kidney suggests that AQP-1 is important for fluid equilibrium and/or drainage in the developing kidney or, alternatively, plays a role in the regulation of growth and/or branching of the vascular tree during kidney development.

Glucocorticoid impairs growth of kidney outer medulla and accelerates loop of Henle differentiation and urinary concentrating capacity in rat kidney development

2006 ◽  
Vol 291 (4) ◽  
pp. F812-F822 ◽  
Author(s):  
Jane Stubbe ◽  
Kirsten Madsen ◽  
Finn Thomsen Nielsen ◽  
Ole Skøtt ◽  
Boye L. Jensen
Keyword(s):  
Kidney Development ◽  
Rat Kidney ◽  
Nuclear Antigen ◽  
Thick Ascending Limb ◽  
Protein Abundance ◽  
Suckling Period ◽  
Outer Medulla ◽  
Rat Pups ◽  
Urinary Concentrating Ability ◽  
And Function

In the rat, urinary concentrating ability develops progressively during the third postnatal (P) week and nearly reaches adult level at weaning ( P21) governed by a rise in circulating glucocorticoid. Elevated extracellular osmolality can lead to growth arrest of epithelial cells. We tested the hypothesis that supranormal exposure of rat pups to glucocorticoid before the endogenous surge enhances urinary concentrating ability but inhibits renomedullary cell proliferation. Proliferating-cell nuclear antigen (PCNA)-positive cells shifted from the nephrogenic zone in the first postnatal week to Tamm-Horsfall-positive thick ascending limb (TAL) cells at the corticomedullary junction at P10– 14. Renal PCNA protein abundance was stable in the suckling period and decreased 10-fold after weaning. Renal PCNA protein abundance decreased in response to dexamethasone (DEXA; 100 μg·kg−1·day−1, P8–12). Prolonged administration of DEXA ( P1-P11) reduced selectively the area and thickness of the outer medulla and the number of PCNA-positive cells. DEXA ( P8– 12) increased urinary and papillary osmolality in normohydrated and water-deprived pups and led to osmotic equilibrium between interstitium and urine, whereas apoptotic and GADD153-positive cells increased in the inner medulla. TAL-associated NaCl transporters Na-K-2Cl cotransporter, Na-K-ATPase-α1, Na/H exchanger type 3, and ROMK increased significantly at weaning and in response to DEXA. We conclude that a low level of circulating glucocorticoid is permissive for proliferation of Henle's loop and the outer medulla before weaning. A reduced papillary tonicity is a crucial factor for the reduced capacity to concentrate urine during postnatal kidney development. We speculate that supranormal exposure to glucocorticoid in the suckling period can alter kidney medullary structure and function permanently.

scholarly journals MIR822 modulates monosporic female gametogenesis through an ARGONAUTE9-dependent pathway in Arabidopsis thaliana

2021 ◽  
Author(s):  
ANDREA TOVAR AGUILAR ◽  
Daniel GRIMANELLI ◽  
Gerardo Acosta Garcia ◽  
Jean Philippe Vielle Calzada ◽  
Jesus Agustin Badillo-Corona ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Flowering Plants ◽  
Loss Of Function ◽  
Genes Encoding ◽  
Functional Megaspore ◽  
Dependent Pathway ◽  
Female Gametogenesis

In the ovule of flowering plants, the establishment of the haploid generation occurs when a somatic cell differentiates into a Megaspore Mother Cell (MMC) and initiates meiosis. As most flowering plants, Arabidopsis thaliana undergoes a monosporic type of gametogenesis; three meiotically derived cells degenerate without further division, and a single one, the functional megaspore (FM), divides mitotically to form the female gametophyte. In Arabidopsis, the ARGONAUTE4 clade proteins are involved in the control of megasporogenesis. In particular, mutations in ARGONAUTE9 (AGO9) lead to the ectopic differentiation of gametic precursors that can give rise female gametophytes. However, the genetic basis and molecular mechanisms that control monosporic gametogenesis remain largely unknown. Here, we show that Arabidopsis plants carrying loss-of-function mutations in the AGO9-interacting miR822a give rise to extranumerary surviving megaspores that acquire a FM identity and divide without giving rise to differentiated female gametophytes. The overexpression of three miR822a target genes encoding Cysteine/Histidine-Rich C1 domain proteins (DC1) phenocopy mir822a plants. The miR822a targets are overexpressed in ago9 mutant ovules, confirming that miR822a acts through an AGO9-dependent pathway to negatively regulate DC1 domain proteins. Our results identify a new role of miRNAs in the most prevalent form of female gametogenesis in flowering plants

scholarly journals (Pro)renin Receptor in Kidney Development and Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Renfang Song ◽  
Ihor V. Yosypiv
Keyword(s):  
Molecular Mechanisms ◽  
Kidney Development ◽  
Critical Role ◽  
Renin Angiotensin System ◽  
Vascular Abnormalities ◽  
Genes Encoding ◽  
Duplicated Collecting System ◽  
Renal Tubular ◽  
Renal Vascular

The renin-angiotensin system (RAS), a key regulator of the blood pressure and fluid/electrolyte homeostasis, also plays a critical role in kidney development. All the components of the RAS are expressed in the developing metanephros. Moreover, mutations in the genes encoding components of the RAS in mice or humans are associated with a broad spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). These forms of CAKUT include renal papillary hypoplasia, hydronephrosis, duplicated collecting system, renal tubular dysgenesis, renal vascular abnormalities, and aberrant glomerulogenesis. Emerging evidence indicates that (pro)renin receptor (PRR), a novel component of the RAS, is essential for proper kidney development and that aberrant PRR signaling is causally linked to cardiovascular and renal disease. This paper describes the role of the RAS in kidney development and highlights emerging insights into the cellular and molecular mechanisms by which the PRR may regulate this critical morphogenetic process.

Impaired urinary concentrating ability and cyclic AMP in K+-depleted rat kidney

1976 ◽  
Vol 231 (4) ◽  
pp. 1204-1208 ◽  
Author(s):  
N Beck ◽  
SK Webster
Keyword(s):  
Cyclic Amp ◽  
Rat Kidney ◽  
Renal Medulla ◽  
Pathogenic Role ◽  
Amp System ◽  
Urinary Cyclic Amp ◽  
Urinary Concentrating Ability ◽  
K Depletion ◽  
Concentrating Defect

The possibility that an alteration of the vasopressin-dependent cyclic AMP system plays a pathogenic role in the urinary concentrating defect in K+ depletion was investigated in the rat. The antidiuretic response to vasopressin was significantly less in K+-depleted rats. In these K+-depleted rats, the increase in urinary cyclic AMP excretion in response to vasopressin was also significantly less. However, repletion of K+ for 1 wk by feeding high-K+ diets restored the ability to increase urinary cyclic AMP excretion in response to vasopressin. In the in vitro incubation of renal medullary slices, the increase in cyclic AMP concentration in response to vasopressin was also significantly less in the slices obtained from K+-depleted rats than in those obtained from control rats. These findings suggest that, in K+ depletion, there is a reversible impairment of the vasopressin-dependent cyclic AMP system in the renal medulla; this impairment may play a pathogenic role in the urinary concentrating defect in K+ depletion.

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