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Distal Nephron

Martina Tetti, Silvia Monticone, Jacopo Burrello, Patrizia Matarazzo, Franco Veglio, Barbara Pasini, Xavier Jeunemaitre, Paolo Mulatero
Liddle syndrome is an inherited form of low-renin hypertension, transmitted with an autosomal dominant pattern. The molecular basis of Liddle syndrome resides in germline mutations of the SCNN1A , SCNN1B and SCNN1G genes, encoding the α, β, and γ-subunits of the epithelial Na⁺ channel (ENaC), respectively. To date, 31 different causative mutations have been reported in 72 families from four continents. The majority of the substitutions cause an increased expression of the channel at the distal nephron apical membrane, with subsequent enhanced renal sodium reabsorption...
March 11, 2018: International Journal of Molecular Sciences
Peng Wu, Zhong-Xiuzi Gao, Xin-Peng Duan, Xiao-Tong Su, Ming-Xiao Wang, Dao-Hong Lin, Ruimin Gu, Wen-Hui Wang
AT2R (AngII [angiotensin II] type 2 receptor) is expressed in the distal nephrons. The aim of the present study is to examine whether AT2R regulates NCC (Na-Cl cotransporter) and Kir4.1 of the distal convoluted tubule. AngII inhibited the basolateral 40 pS K channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule treated with losartan but not with PD123319. AT2R agonist also inhibits the K channel, indicating that AT2R was involved in tonic regulation of Kir4.1. The infusion of PD123319 stimulated the expression of tNCC (total NCC) and pNCC (phosphorylated NCC; Thr53 ) by a time-dependent way with the peak at 4 days...
February 26, 2018: Hypertension
Chloé Rafael, Christelle Soukaseum, Véronique Baudrie, Perrine Frère, Juliette Hadchouel
Mutations of the gene encoding WNK1 [With No lysine (K) kinase 1] or WNK4 cause Familial Hyperkalemic Hypertension (FHHt). Previous studies have shown that the activation of SPAK (Ste20-related Proline/Alanine-rich Kinase) plays a dominant role in the development of FHHt caused by WNK4 mutations. The implication of SPAK in FHHt caused by WNK1 mutation has never been investigated. To clarify this issue, we crossed WNK1+/FHHt mice with SPAK knock-in mice in which the T-loop Thr243 residue was mutated to alanine to prevent activation by WNK kinases...
February 19, 2018: Scientific Reports
Nils O Lindström, Tracy Tran, Jinjin Guo, Elisabeth Rutledge, Riana K Parvez, Matthew E Thornton, Brendan Grubbs, Jill A McMahon, Andrew P McMahon
The nephron is the functional unit of the kidney, but the mechanism of nephron formation during human development is unclear. We conducted a detailed analysis of nephron development in humans and mice by immunolabeling, and we compared human and mouse nephron patterning to describe conserved and divergent features. We created protein localization maps that highlight the emerging patterns along the proximal-distal axis of the developing nephron and benchmark expectations for localization of functionally important transcription factors, which revealed unanticipated cellular diversity...
February 15, 2018: Journal of the American Society of Nephrology: JASN
J A Quadri, S Sarwar, A Sinha, M Kalaivani, A K Dinda, A Bagga, T S Roy, T K Das, A Shariff
The susceptibility of the kidneys to fluoride toxicity can largely be attributed to its anatomy and function. As the filtrate moves along the complex tubular structure of each nephron, it is concentrated in the proximal and distal tubules and collecting duct. It has been frequently observed that the children suffering from renal impairments also have some symptoms of dental and skeletal fluorosis. The findings suggest that fluoride somehow interferes with renal anatomy and physiology, which may lead to renal pathogenesis...
January 1, 2018: Human & Experimental Toxicology
Ryan W Walker, Shijia Zhang, Joycelynn A Coleman-Barnett, L Lee Hamm, Kathleen S Hering-Smith
The calcium sensing receptor (CaSR) in the distal nephron decreases the propensity for calcium stones. Here we investigate if the apical CaSR in the proximal tubule also prevents stone formation acting via regulation of apical dicarboxylate and citrate transport. Urinary citrate, partially reabsorbed as a dicarboxylate in the proximal tubule lumen, inhibits stone formation by complexing calcium. We previously demonstrated a novel apical calcium-sensitive dicarboxylate transport system in OK proximal tubule cells...
January 30, 2018: Urolithiasis
Lori L O'Brien, Qiuyu Guo, Emad Bahrami-Samani, Joo-Seop Park, Sean M Hasso, Young-Jin Lee, Alan Fang, Albert D Kim, Jinjin Guo, Trudy M Hong, Kevin A Peterson, Scott Lozanoff, Ramya Raviram, Bing Ren, Ben Fogelgren, Andrew D Smith, Anton Valouev, Andrew P McMahon
Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated 'regulatory hotspots' around genes closely associated with progenitor programs...
January 29, 2018: PLoS Genetics
Emilie Boscardin, Romain Perrier, Chloé Sergi, Marc P Maillard, Johannes Loffing, Dominique Loffing-Cueni, Robert Koesters, Bernard C Rossier, Edith Hummler
The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the αENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of αENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa+)/low potassium (LK+) rescue diet...
January 25, 2018: Journal of the American Society of Nephrology: JASN
Michael B Butterworth
No abstract text is available yet for this article.
January 24, 2018: American Journal of Physiology. Renal Physiology
Lauren Grace Douma, Meaghan Rayann Holzworth, Kristen Solocinski, Sarah Howland Masten, Amber Holly Miller, Kit-Yan Cheng, I Jeanette Lynch, Brian D Cain, Charles S Wingo, Michelle L Gumz
Many physiological functions have a circadian rhythm, including blood pressure (BP). BP is highest during the active phase whereas during the rest period BP dips 10%-20%. Patients that do not experience this dip at night are termed "non-dippers." Non-dipping hypertension is associated with increased risk of cardiovascular disease. The mechanisms underlying non-dipping hypertension are not understood. Without the circadian clock gene Per1, C57BL/6J mice develop non-dipping hypertension on a high-salt diet plus mineralocorticoid treatment (HS/DOCP)...
January 10, 2018: American Journal of Physiology. Renal Physiology
William C Valinsky, Rhian M Touyz, Alvin Shrier
Hyperaldosteronism, a common cause of hypertension, is strongly connected to Na+, K+, and Mg2+ dysregulation. Owing to its steroidal structure, aldosterone is an active transcriptional modifier when bound to the mineralocorticoid receptor (MR) in cells expressing the enzyme 11β-hydroxysteroid dehydrogenase 2, such as those comprising the aldosterone-sensitive distal nephron (ASDN). One such up-regulated protein, the ubiquitous serum and glucocorticoid regulated kinase 1 (SGK1), has the capacity to modulate the surface expression and function of many classes of renal ion channels, including those that transport Na+ (ENaC), K+ (ROMK/BK), Ca2+ (TRPV4/5/6), Mg2+ (TRPM7/6), and Cl- (ClC-K, CFTR)...
January 31, 2018: Clinical Science (1979-)
Francesco Trepiccione, Federica Prosperi, Luigi Regenburgh de la Motte, Christian A Hübner, Regine Chambrey, Dominique Eladari, Giovambattista Capasso
Background: Distal renal tubular acidosis (dRTA) is characterized by an impairment of the urinary acidification process in the distal nephron. Complete or incomplete metabolic acidosis coupled with inappropriately alkaline urine are the hallmarks of this condition. Genetic forms of dRTA are caused by loss of function mutations of either SLC4A1 , encoding the AE1 anion exchanger, or ATP6V1B1 and ATP6V0A4 , encoding for the B1 and a4 subunits of the vH+ ATPase, respectively. These genes are crucial for the function of A-type intercalated cells (A-IC) of the distal nephron...
December 2017: Kidney Diseases
Samuel N Heyman, Zaid Abassi, Christian Rosenberger, Hiba Yaseen, Galia Skarjinski, Ahuva Shina, Susanne Mathia, Natalia Krits, Mogher Khamaisi
AIM: Cyclosporine A (CsA) induces renal vasoconstriction and hypoxia and enhances the expression of endothelin-1 (ET-1) pro-hormone (pre-pro ET-1), plausibly leading to a feed-forward loop of renal vasoconstriction, hypoxia, and enhanced synthesis of the potent vasoconstrictor ET-1. Endothelin converting enzyme (ECE)-1 cleaves big endothelin to generate endothelin (ET)-1 and is up-regulated by hypoxia via hypoxia-inducible factor (HIF). We hypothesized that in addition to the direct induction of ET-1 synthesis, CsA might also intensify renal ECE-1expression, thus contributing to enhanced ET-1 synthesis following CsA...
January 13, 2018: Acta Physiologica
Susan M Wall
Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl- absorption and HCO3 - secretion largely through pendrin-dependent Cl- /HCO3 - exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO3 administration. In some rodent models, pendrin-mediated HCO3 - secretion modulates acid-base balance...
December 2017: Kidney Research and Clinical Practice
Biff F Palmer, Deborah J Clegg
Hyperkalemia results either from the shift of potassium out of cells or from abnormal renal potassium excretion. Cell shift leads to transient increases in the plasma potassium concentration, whereas decreased renal excretion of potassium leads to sustained hyperkalemia. Impairments in renal potassium excretion can be the result of reduced sodium delivery to the distal nephron, decreased mineralocorticoid level or activity, or abnormalities in the cortical collecting duct. In some instances, all 3 of these perturbations are present...
December 2017: Cleveland Clinic Journal of Medicine
Christian Hinze, Janett Ruffert, Katharina Walentin, Nina Himmerkus, Elham Nikpey, Olav Tenstad, Helge Wiig, Kerim Mutig, Zeliha Yesim Yurtdas, Janet D Klein, Jeff M Sands, Federica Branchi, Michael Schumann, Sebastian Bachmann, Markus Bleich, Kai M Schmidt-Ott
Collecting ducts make up the distal-most tubular segments of the kidney, extending from the cortex, where they connect to the nephron proper, into the medulla, where they release urine into the renal pelvis. During water deprivation, body water preservation is ensured by the selective transepithelial reabsorption of water into the hypertonic medullary interstitium mediated by collecting ducts. The collecting duct epithelium forms tight junctions composed of barrier-enforcing claudins and exhibits a higher transepithelial resistance than other segments of the renal tubule exhibit...
December 13, 2017: Journal of the American Society of Nephrology: JASN
Anjali Aggarwal, David Rodriguez-Buritica
Hypertension (HT) is a public health problem in children particularly related to the epidemic of overweight and obesity. Monogenic forms of HT are important in the differential diagnosis in children presenting with severe or refractory HT, who have a family history of early-onset HT, unusual physical examination findings, and/or characteristic hormonal and biochemical abnormalities. Most genetic defects in these disorders ultimately result in increased sodium transport in the distal nephron resulting in volume expansion and HT...
November 2017: Advances in Chronic Kidney Disease
Alejandro Suárez-Bonnet, Ana Lara-García, Alexander L Stoll, Sofia Carvalho, Simon L Priestnall
14-3-3σ is a protein expressed in many epithelial tissues associated with essential cell functions, including cell-cycle control, apoptosis, and cytoskeletal integrity. There is a paucity of knowledge of the tumorigenesis of canine renal cell carcinomas (RCCs), and the histological origin of this tumor has not been established. This study analyzed the expression of 14-3-3σ, Ki-67, cytokeratins, and vimentin in 40 canine RCCs. Aberrant expression of 14-3-3σ was demonstrated in 15 (38%) cases and was associated with a significantly shorter survival time ( P < ...
January 1, 2017: Veterinary Pathology
B P Ilenwabor, E O Asowata, L F Obika
The mineralocorticoid aldosterone is widely accepted as a key regulator of K+ balance as well as urinary K+excretion. However, recent evidence suggests that the circadian control of K+ excretion is independent of aldosterone. Thedelivery of Na+ to the distal nephron is known to be an important determinant of aldosterone mediated secretion of K+ in thissegment of the nephron. Examining the link between distal Na+ delivery and K+ excretion; and how this link affect circadianK+ excretion will advance what is currently known about the maintenance of K+ homeostasis...
June 30, 2017: Nigerian Journal of Physiological Sciences: Official Publication of the Physiological Society of Nigeria
Thomas R Kleyman, Ossama B Kashlan, Rebecca P Hughey
Epithelial Na+ channels (ENaCs) are members of the ENaC/degenerin family of ion channels that evolved to respond to extracellular factors. In addition to being expressed in the distal aspects of the nephron, where ENaCs couple the absorption of filtered Na+ to K+ secretion, these channels are found in other epithelia as well as nonepithelial tissues. This review addresses mechanisms by which ENaC activity is regulated by extracellular factors, including proteases, Na+ , and shear stress. It also addresses other factors, including acidic phospholipids and modification of ENaC cytoplasmic cysteine residues by palmitoylation, which enhance channel activity by altering interactions of the channel with the plasma membrane...
February 10, 2018: Annual Review of Physiology
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