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Distal Nephron

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https://www.readbyqxmd.com/read/28331059/adaptive-changes-in-gfr-tubular-morphology-and-transport-in-subtotal-nephrectomized-kidneys-modeling-and-analysis
#1
Anita T Layton, Aurélie Edwards, Volker Vallon
Removal of renal mass stimulates anatomical and functional adaptations in the surviving nephrons, including elevation in single-nephron glomerular filtration rate (SNGFR) and tubular hypertrophy. A goal of this study is to assess the extent to which the concomitant increases in filtered load and tubular transport capacity preserve homeostasis of water and salt. To accomplish that goal, we developed computational models to simulate solute transport and metabolism along nephron populations in a uninephrectomized (UNX) rat and a 5/6-nephrectomized (5/6-NX) rat...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28315934/gas1-expression-in-parietal-cells-of-bowman-s-capsule-in-experimental-diabetic-nephropathy
#2
Brenda I Luna-Antonio, Rafael Rodriguez-Muñoz, Carmen Namorado-Tonix, Paula Vergara, Jose Segovia, Jose L Reyes
Gas1 (Growth Arrest-Specific 1) is a pleiotropic protein with novel functions including anti-proliferative and proapoptotic activities. In the kidney, the expression of Gas1 has been described in mesangial cells. In this study, we described that renal parietal cells of Bowman's capsule (BC) and the distal nephron cells also express Gas1. The role of Gas1 in the kidney is not yet known. There is a subpopulation of progenitor cells in Bowman's capsule with self-renewal properties which can eventually differentiate into podocytes as a possible mechanism of regeneration in the early stages of diabetic nephropathy...
March 18, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28289184/renal-tubular-ubiquitin-protein-ligase-nedd4-2-is-required-for-renal-adaptation-during-long-term-potassium-depletion
#3
Lama Al-Qusairi, Denis Basquin, Ankita Roy, Renuga Devi Rajaram, Marc P Maillard, Arohan R Subramanya, Olivier Staub
Adaptation of the organism to potassium (K(+)) deficiency requires precise coordination among organs involved in K(+) homeostasis, including muscle, liver, and kidney. How the latter performs functional and molecular changes to ensure K(+) retention is not well understood. Here, we investigated the role of ubiquitin-protein ligase NEDD4-2, which negatively regulates the epithelial sodium channel (ENaC), Na(+)/Cl(-) cotransporter (NCC), and with no-lysine-kinase 1 (WNK1). After dietary K(+) restriction for 2 weeks, compared with control littermates, inducible renal tubular NEDD4-2 knockout (Nedd4L(Pax8/LC1) ) mice exhibited severe hypokalemia and urinary K(+) wasting...
March 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28289181/hypokalemia-and-pendrin-induction-by-aldosterone
#4
Ning Xu, Daigoro Hirohama, Kenichi Ishizawa, Wen Xiu Chang, Tatsuo Shimosawa, Toshiro Fujita, Shunya Uchida, Shigeru Shibata
Aldosterone plays an important role in regulating Na-Cl reabsorption and blood pressure. Epithelial Na(+) channel, Na(+)-Cl(-) cotransporter, and Cl(-)/HCO3(-) exchanger pendrin are the major mediators of Na-Cl transport in the aldosterone-sensitive distal nephron. Existing evidence also suggests that plasma K(+) concentration affects renal Na-Cl handling. In this study, we posited that hypokalemia modulates the effects of aldosterone on pendrin in hyperaldosteronism. Chronic aldosterone infusion in mice increased pendrin levels at the plasma membrane, and correcting hypokalemia in this model almost completely blocked pendrin upregulation...
March 13, 2017: Hypertension
https://www.readbyqxmd.com/read/28252422/sorption-correction-of-nephron-sub-microscopic-changes-caused-by-neoplastic-chronic-intoxication-with-the-application-of-cytostatic-therapy
#5
Yu Soroka, N Lisnychuk, I Demkiv, O Oleshchuk
The electron microscopic changes of the nephron structural components under conditions of dimethylhydrazine (DMH)-induced carcinogenesis with the development of colorectal adenocarcinoma in situ were evaluated. Destructive changes in epitheliocytes of proximal and distal tubules of the nephron, microcirculation disturbances in renal corpuscles and tubular structure are evidences of disorder in urine formation stages. Аdministration of cytostatics aggravates the degree of destructive changes in the kidney. The application of carbon enterosorbent of IV generation "Carboline" for chronic neoplastic endotoxemia correction in combination with chemotherapy components significantly reduces the structural changes of the cortical substance of the kidneys, activates processes of reparative regeneration...
January 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28242715/unraveling-the-physiology-of-pro-renin-receptor-in-the-distal-nephron
#6
Tianxin Yang
No abstract text is available yet for this article.
February 27, 2017: Hypertension
https://www.readbyqxmd.com/read/28187982/the-renal-trpv4-channel-is-essential-for-adaptation-to-increased-dietary-potassium
#7
Mykola V Mamenko, Nabila Boukelmoune, Viktor N Tomilin, Oleg L Zaika, V Behrana Jensen, Roger G O'Neil, Oleh M Pochynyuk
To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This process involves stimulation of calcium-activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct. Recent evidence suggests that the TRPV4 channel is a critical determinant of flow-dependent intracellular calcium elevations in these segments of the renal tubule. Here, we demonstrate that elevated dietary potassium intake (five percent potassium) increases renal TRPV4 mRNA and protein levels in an aldosterone-dependent manner and causes redistribution of the channel to the apical plasma membrane in native collecting duct cells...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28179254/a-mathematical-model-of-the-rat-kidney-k-induced-natriuresis
#8
Alan M Weinstein
A model of the rat nephron (Am. J. Physiol. 308:F1098, 2015) has been extended with addition of medullary vasculature. Blood vessels contain solutes from the nephron model, plus additional species from the model of Atherton et al. (Am. J. Physiol. 247:F61, 1984), representing hemoglobin buffering. In contrast to prior models of the urine concentrating mechanism, reflection coefficients for DVR are near zero. Model unknowns are initial proximal tubule pressures and flows, connecting tubule pressure, and medullary interstitial pressures and concentrations...
February 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28154191/specific-palmitoyltransferases-associate-with-and-activate-the-epithelial-sodium-channel
#9
Anindit Mukherjee, Zhijian Wang, Carol L Kinlough, Paul A Poland, Allison L Marciszyn, Nicolas Montalbetti, Marcelo D Carattino, Michael B Butterworth, Thomas R Kleyman, Rebecca P Hughey
The epithelial sodium channel (ENaC) has an important role in regulating extracellular fluid volume and blood pressure, as well as airway surface liquid volume and mucociliary clearance. ENaC is a trimer of three homologous subunits (α, β, and γ). We previously reported that cytoplasmic residues on the β (βCys-43 and βCys-557) and γ (γCys-33 and γCys-41) subunits are palmitoylated. Mutation of Cys that blocked ENaC palmitoylation also reduced channel open probability. Furthermore, γ subunit palmitoylation had a dominant role over β subunit palmitoylation in regulating ENaC...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100643/fluid-shear-stress-increases-transepithelial-transport-of-ca2-in-ciliated-distal-convoluted-and-connecting-tubule-cells
#10
Sami G Mohammed, Francisco J Arjona, Femke Latta, René J M Bindels, Ronald Roepman, Joost G J Hoenderop
In kidney, transcellular transport of Ca(2+) is mediated by transient receptor potential vanilloid 5 and Na(+)-Ca(2+) exchanger 1 proteins in distal convoluted and connecting tubules (DCT and CNT, respectively). It is not yet understood how DCT/CNT cells can adapt to differences in tubular flow rate and, consequently, Ca(2+) load. This study aims to elucidate the molecular mechanisms by which DCT/CNT cells sense fluid dynamics to control transepithelial Ca(2+) reabsorption and whether their primary cilia play an active role in this process...
January 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28094030/glucocorticoid-induced-leucine-zipper-protein-regulates-sodium-and-potassium-balance-in-the-distal-nephron
#11
Priyanka Rashmi, GianLuca Colussi, Michael Ng, Xinhao Wu, Atif Kidwai, David Pearce
Glucocorticoid induced leucine zipper protein (GILZ) is an aldosterone-regulated protein that controls sodium transport in cultured kidney epithelial cells. Mice lacking GILZ have been reported previously to have electrolyte abnormalities. However, the mechanistic basis has not been explored. Here we provide evidence supporting a role for GILZ in modulating the balance of renal sodium and potassium excretion by regulating the sodium-chloride cotransporter (NCC) activity in the distal nephron. Gilz(-/-) mice have a higher plasma potassium concentration and lower fractional excretion of potassium than wild type mice...
January 13, 2017: Kidney International
https://www.readbyqxmd.com/read/28092112/aquaporin-2-excretion-in-hospitalized-patients-with-cirrhosis-relation-to-development-of-renal-insufficiency-and-mortality
#12
Troels M Busk, Søren Møller, Erling B Pedersen, Alexander Gerbes, Aleksander Krag, Markus Peck-Radosavljevic, Sona Frankova, Minneke J Coenraad, Flemming Bendtsen
BACKGROUND AND AIM: Urinary aquaporin-2 (AQP2) is a parameter of water transport in the principal cells in the distal part of the nephron and involved in water retention in cirrhosis and may be a marker of renal function. The aim of the study was to evaluate AQP2 as a predictor of renal insufficiency and death in patients with cirrhosis. METHODS: Urine samples from 199 patients (90 patients without organ failure (Group 1), 58 patients with organ failure excluding renal failure (Group 2) and 51 patients with organ failure including renal failure (Group 3)) from the CANONIC study were analyzed for urine AQP2 and urine osmolality...
November 7, 2016: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28064162/acute-genetic-ablation-of-pendrin-lowers-blood-pressure-in-mice
#13
Francesco Trepiccione, Christelle Soukaseum, Veronique Baudrie, Yusuke Kumai, Jacques Teulon, Bruno Villoutreix, Nicolas Cornière, Philine Wangemann, Andrew J Griffith, Yoon Byung Choi, Juliette Hadchouel, Regine Chambrey, Dominique Eladari
BACKGROUND: Pendrin, the chloride/bicarbonate exchanger of β-intercalated cells of the renal connecting tubule and the collecting duct, plays a key role in NaCl reabsorption by the distal nephron. Therefore, pendrin may be important for the control of extracellular fluid volume and blood pressure. METHODS: Here, we have used a genetic mouse model in which the expression of pendrin can be switched-on in vivo by the administration of doxycycline. Pendrin can also be rapidly removed when doxycycline administration is discontinued...
January 7, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28003189/involvement-of-enac-in-the-development-of-salt-sensitive-hypertension
#14
Tengis S Pavlov, Alexander Staruschenko
Salt-sensitive hypertension is associated with renal and vascular dysfunctions which lead to impaired fluid excretion, increased cardiac output and total peripheral resistance. It is commonly accepted that increased renal sodium handling and plasma volume expansion are necessary factors for the development of salt-induced hypertension. The epithelial sodium channel (ENaC) is a trimeric ion channel expressed in the distal nephron which plays a critical role in the regulation of sodium reabsorption in both normal and pathological conditions...
December 21, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28002260/regulation-of-sodium-balance-in-the-distal-nephron-urinary-exosomes-contribute-to-knowledge
#15
Richard D Gordon
No abstract text is available yet for this article.
February 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/27996936/prostaglandin-signaling-regulates-nephron-segment-patterning-of-renal-progenitors-during-zebrafish-kidney-development
#16
Shahram Jevin Poureetezadi, Christina N Cheng, Joseph M Chambers, Bridgette E Drummond, Rebecca A Wingert
Kidney formation involves patterning events that induce renal progenitors to form nephrons with an intricate composition of multiple segments. Here, we performed a chemical genetic screen using zebrafish and discovered that prostaglandins, lipid mediators involved in many physiological functions, influenced pronephros segmentation. Modulating levels of prostaglandin E2 (PGE2) or PGB2 restricted distal segment formation and expanded a proximal segment lineage. Perturbation of prostaglandin synthesis by manipulating Cox1 or Cox2 activity altered distal segment formation and was rescued by exogenous PGE2...
December 20, 2016: ELife
https://www.readbyqxmd.com/read/27932475/intercalated-cell-depletion-and-vacuolar-h-atpase-mistargeting-in-an-ae1-r607h-knockin-model
#17
Rizwan Mumtaz, Francesco Trepiccione, J Christopher Hennings, Antje K Huebner, Bettina Serbin, Nicolas Picard, A K M Shahid Ullah, Teodor G Păunescu, Diane E Capen, Rawad M Lashhab, Isabelle Mouro-Chanteloup, Seth L Alper, Carsten A Wagner, Emmanuelle Cordat, Dennis Brown, Dominique Eladari, Christian A Hübner
Distal nephron acid secretion is mediated by highly specialized type A intercalated cells (A-ICs), which contain vacuolar H(+)-ATPase (V-type ATPase)-rich vesicles that fuse with the apical plasma membrane on demand. Intracellular bicarbonate generated by luminal H(+) secretion is removed by the basolateral anion-exchanger AE1. Chronically reduced renal acid excretion in distal renal tubular acidosis (dRTA) may lead to nephrocalcinosis and renal failure. Studies in MDCK monolayers led to the proposal of a dominant-negative trafficking mechanism to explain AE1-associated dominant dRTA...
December 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27915449/common-variants-in-cldn14-are-associated-with-differential-excretion-of-magnesium-over-calcium-in-urine
#18
REVIEW
Tanguy Corre, Eric Olinger, Sarah E Harris, Michela Traglia, Sheila Ulivi, Stefania Lenarduzzi, Hendrica Belge, Sonia Youhanna, Natsuko Tokonami, Olivier Bonny, Pascal Houillier, Ozren Polasek, Ian J Deary, John M Starr, Daniela Toniolo, Paolo Gasparini, Peter Vollenweider, Caroline Hayward, Murielle Bochud, Olivier Devuyst
The nature and importance of genetic factors regulating the differential handling of Ca(2+) and Mg(2+) by the renal tubule in the general population are poorly defined. We conducted a genome-wide meta-analysis of urinary magnesium-to-calcium ratio to identify associated common genetic variants. We included 9320 adults of European descent from four genetic isolates and three urban cohorts. Urinary magnesium and calcium concentrations were measured centrally in spot urine, and each study conducted linear regression analysis of urinary magnesium-to-calcium ratio on ~2...
January 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27909897/nha2-is-expressed-in-distal-nephron-and-regulated-by-dietary-sodium
#19
Kalyan C Kondapalli, R Todd Alexander, Jennifer L Pluznick, Rajini Rao
Increased renal reabsorption of sodium is a significant risk factor in hypertension. An established clinical marker for essential hypertension is elevated sodium lithium countertransport (SLC) activity. NHA2 is a newly identified Na(+)(Li(+))/H(+) antiporter with potential genetic links to hypertension, which has been shown to mediate SLC activity and H(+)-coupled Na(+)(Li(+)) efflux in kidney-derived MDCK cells. To evaluate a putative role in sodium homeostasis, we determined the effect of dietary salt on NHA2...
December 1, 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27899376/gwas-of-clinically-defined-gout-and-subtypes-identifies-multiple-susceptibility-loci-that-include-urate-transporter-genes
#20
Akiyoshi Nakayama, Hirofumi Nakaoka, Ken Yamamoto, Masayuki Sakiyama, Amara Shaukat, Yu Toyoda, Yukinori Okada, Yoichiro Kamatani, Takahiro Nakamura, Tappei Takada, Katsuhisa Inoue, Tomoya Yasujima, Hiroaki Yuasa, Yuko Shirahama, Hiroshi Nakashima, Seiko Shimizu, Toshihide Higashino, Yusuke Kawamura, Hiraku Ogata, Makoto Kawaguchi, Yasuyuki Ohkawa, Inaho Danjoh, Atsumi Tokumasu, Keiko Ooyama, Toshimitsu Ito, Takaaki Kondo, Kenji Wakai, Blanka Stiburkova, Karel Pavelka, Lisa K Stamp, Nicola Dalbeth, Yutaka Sakurai, Hiroshi Suzuki, Makoto Hosoyamada, Shin Fujimori, Takashi Yokoo, Tatsuo Hosoya, Ituro Inoue, Atsushi Takahashi, Michiaki Kubo, Hiroshi Ooyama, Toru Shimizu, Kimiyoshi Ichida, Nariyoshi Shinomiya, Tony R Merriman, Hirotaka Matsuo
OBJECTIVE: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. METHODS: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study...
November 29, 2016: Annals of the Rheumatic Diseases
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