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Distal Nephron

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https://www.readbyqxmd.com/read/27909897/nha2-is-expressed-in-distal-nephron-and-regulated-by-dietary-sodium
#1
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
#2
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
https://www.readbyqxmd.com/read/27895120/ankyrin-g-expression-regulates-apical-delivery-of-the-epithelial-sodium-channel-enac
#3
Christine A Klemens, Robert S Edinger, Lindsay Kightlinger, Xiaoning Liu, Michael B Butterworth
The epithelial sodium channel (ENaC) is the limiting entry point for Na(+) reabsorption in the distal kidney nephron and is regulated by numerous hormones, including the mineralocorticoid hormone aldosterone. Previously we identified ankyrin G (AnkG), a cytoskeletal protein involved in vesicular transport, as a novel aldosterone-induced protein that can alter Na(+) transport in mouse cortical collecting duct (mCCD) cells. However, the mechanisms underlying AnkG's regulation of Na(+) transport were unknown. Here we report that AnkG expression directly regulates Na(+) transport by altering ENaC activity in the apical membrane...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27814606/regulation-and-function-of-renal-medullary-cyclooxygenase-2-during-high-salt-loading
#4
Tianxin Yang, Mi Liu
Prostaglandins (PGs) are important autocrine/paracrine regulators that contribute to sodium balance and blood pressure control. Along the nephron, the highest amount of PGE2 is found in the distal nephron, an important site for fine-tuning of urinary sodium and water excretion. Cylooxygenase-2 (COX-2) is abundantly expressed in the renal medulla and its expression along with urinary PGE2 excretion is highly induced by chronic salt loading. Factors involved in high salt-induced COX-2 expression in the renal medulla include the hypertonicity, fluid shear stress (FSS), and hypoxia-inducible factor-1 alpha (HIF-1 alpha)...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27806944/the-mechanosensitive-bk%C3%AE-%C3%AE-1-channel-localizes-to-cilia-of-principal-cells-in-rabbit-cortical-collecting-duct-ccd
#5
Rolando Carrisoza-Gaytán, Lijun Wang, Carlos M N Schreck, Thomas R Kleyman, Wen-Hui Wang, Lisa M Satlin
Within the CCD of the distal nephron of the rabbit, the BK (maxi K) channel mediates Ca(2+)- and/or stretch-dependent flow-induced K(+) secretion (FIKS) and contributes to K(+) adaptation in response to dietary K(+) loading. An unresolved question is whether BK channels in intercalated cells (ICs) and/or principal cells (PCs) in the CCD mediate these K(+) secretory processes. In support for a role for ICs in FIKS is the higher density of immunoreactive apical BKα (pore forming subunit) and functional BK channel activity than detected in PCs, and an increase in IC BKα expression in response to a high K(+) diet...
November 2, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27796022/-treatment-of-autosomal-dominant-polycystic-kidney-disease-adpkd-tolvaptan
#6
Massimo Cirillo
The European Medicines Agency approved tolvaptan to slow cyst growth and renal failure progression in adults with ADPKD, glomerular filtration 60 mL/min x 1.73 m2 and rapidly progressive disease. In a multicenter 3-year study, conducted on 1,445 patients with non-genotyped ADPKD, ages 18-50 years, predicted creatinine clearance 60 mL/min and kidney total volume 750 mL, tolvaptan slowed kidney failure progression (-23%-46% for different objectives) and reduced kidney volume increase and pain without effects on hypertension and albuminuria...
September 2016: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/27767102/a-single-nucleotide-polymorphism-in-kidney-anion-exchanger-1-gene-is-associated-with-incomplete-type-1-renal-tubular-acidosis
#7
Takumi Takeuchi, Mami Hattori-Kato, Yumiko Okuno, Atsushi Kanatani, Masayoshi Zaitsu, Koji Mikami
Various conditions including distal renal tubular acidosis (dRTA) can induce stone formation in the kidney. dRTA is characterized by an impairment of urine acidification in the distal nephron. dRTA is caused by variations in genes functioning in intercalated cells including SLC4A1/AE1/Band3 transcribing two kinds of mRNAs encoding the Cl(-)/HCO3(-) exchanger in erythrocytes and that expressed in α-intercalated cells (kAE1). With the acid-loading test, 25% of urolithiasis patients were diagnosed with incomplete dRTA...
October 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27759103/caudal-migration-and-proliferation-of-renal-progenitors-regulates-early-nephron-segment-size-in-zebrafish
#8
Richard W Naylor, Rachel C Dodd, Alan J Davidson
The nephron is the functional unit of the kidney and is divided into distinct proximal and distal segments. The factors determining nephron segment size are not fully understood. In zebrafish, the embryonic kidney has long been thought to differentiate in situ into two proximal tubule segments and two distal tubule segments (distal early; DE, and distal late; DL) with little involvement of cell movement. Here, we overturn this notion by performing lineage-labelling experiments that reveal extensive caudal movement of the proximal and DE segments and a concomitant compaction of the DL segment as it fuses with the cloaca...
October 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27753955/os-08-05-novel-molecular-insights-in-urinary-exosome-protein-profiling-in-thiazide-induced-hyponatremia
#9
Sarath Channavajjhala, Wenjing Jia, Mahli Jalland, Kevin OʼShaughnessy, Ian Hall, Mark Glover
OBJECTIVE: Thiazide diuretics are amongst most widely prescribed and effective anti-hypertensive medicines worldwide. Thiazides however cause Thiazide-Induced Hyponatremia (TIH), a novel and potentially important paradigm of dysregulated distal nephron sodium and water reabsorption. A priori TIH must result from excessive saliuresis and/or water reabsorption. The water and electrolyte transporter composition of Urinary Exosomes (UE) reflects their cellular origin and are a promising way to study renal dysfunction...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753890/ish-nia-os-05-interleukin-6-transactivation-of-the-mineralocorticoid-receptor
#10
Brandi Wynne, Trinity Kronk, Otor Al-Khalili, Benjamin Ko, Franziska Theilig, Douglas Eaton, Robert Hoover
OBJECTIVE: Hypertension is characterized by increased sodium reabsorption along the aldosterone-sensitive distal nephron (ASDN) and systemic inflammation. Interleukin-6 (IL-6) is a possible mediator, signaling via the transmembrane IL-6 receptor alpha (IL-6Rα); however, whether IL-6Rα is present in the distal convoluted tubule (DCT) is unknown. Increased sodium reabsorption is not always correlated with increased aldosterone (Aldo). Thus, understanding how Aldo-independent sodium reabsorption occurs is critical...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27723777/effects-of-torc1-inhibition-during-the-early-and-established-phases-of-polycystic-kidney-disease
#11
Michelle H T Ta, Kristina G Schwensen, Sheryl Foster, Mayuresh Korgaonkar, Justyna E Ozimek-Kulik, Jacqueline K Phillips, Anthony Peduto, Gopala K Rangan
The disease-modifying effects of target of rapamycin complex 1 (TORC1) inhibitors during different stages of polycystic kidney disease (PKD) are not well defined. In this study, male Lewis Polycystic Kidney Disease (LPK) rats (a genetic ortholog of human NPHP9, phenotypically characterised by diffuse distal nephron cystic growth) and Lewis controls received either vehicle (V) or sirolimus (S, 0.2 mg/kg by intraperitoneal injection 5 days per week) during the early (postnatal weeks 3 to 10) or late stages of disease (weeks 10 to 20)...
2016: PloS One
https://www.readbyqxmd.com/read/27681562/the-nephron-pro-renin-receptor-function-and-significance
#12
REVIEW
Nirupama Ramkumar, Donald E Kohan
The (pro)renin receptor (PRR) is a multifunctional protein that is part of the renin-angiotensin system and is an important accessory molecule for the vacuolar H(+)-ATPase. The PRR is widely expressed in the kidney with relatively high abundance in the distal nephron. Determining the physiological relevance of the PRR has been challenging due to early lethality in whole animal and cell-specific PRR knockout models. Recently, viable renal cell-specific PRR knockout mice have been developed; these studies suggest that PRR in the nephron can modulate renal function via angiotensin II (ANG II)-dependent and -independent cell signaling pathways...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27678263/is-hypertension-a-bone-marrow-disease
#13
EDITORIAL
Kim Ramil C Montaniel, David G Harrison
No abstract text is available yet for this article.
November 1, 2016: Circulation
https://www.readbyqxmd.com/read/27666430/matrix-metalloproteinase-20-co-expression-with-dentin-sialophosphoprotein-in-human-and-monkey-kidneys
#14
Kalu U E Ogbureke, Komal Koli, Geetu Saxena
We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively...
October 2016: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/27643350/os-08-05-novel-molecular-insights-in-urinary-exosome-protein-profiling-in-thiazide-induced-hyponatremia
#15
Sarath Channavajjhala, Wenjing Jia, Mahli Jalland, Kevin OʼShaughnessy, Ian Hall, Mark Glover
OBJECTIVE: Thiazide diuretics are amongst most widely prescribed and effective anti-hypertensive medicines worldwide. Thiazides however cause Thiazide-Induced Hyponatremia (TIH), a novel and potentially important paradigm of dysregulated distal nephron sodium and water reabsorption. A priori TIH must result from excessive saliuresis and/or water reabsorption. The water and electrolyte transporter composition of Urinary Exosomes (UE) reflects their cellular origin and are a promising way to study renal dysfunction...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27643236/ish-nia-os-05-interleukin-6-transactivation-of-the-mineralocorticoid-receptor
#16
Brandi Wynne, Trinity Kronk, Otor Al-Khalili, Benjamin Ko, Franziska Theilig, Douglas Eaton, Robert Hoover
OBJECTIVE: Hypertension is characterized by increased sodium reabsorption along the aldosterone-sensitive distal nephron (ASDN) and systemic inflammation. Interleukin-6 (IL-6) is a possible mediator, signaling via the transmembrane IL-6 receptor alpha (IL-6Rα); however, whether IL-6Rα is present in the distal convoluted tubule (DCT) is unknown. Increased sodium reabsorption is not always correlated with increased aldosterone (Aldo). Thus, understanding how Aldo-independent sodium reabsorption occurs is critical...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27636893/a-microrna-cluster-mir-23%C3%A2-24%C3%A2-27-is-upregulated-by-aldosterone-in-the-distal-kidney-nephron-where-it-alters-sodium-transport
#17
X Liu, R S Edinger, C A Klemens, Y L Phua, A J Bodnar, W A LaFramboise, J Ho, M B Butterworth
The epithelial sodium channel (ENaC) is expressed in the epithelial cells of the distal convoluted tubules, connecting tubules and cortical collecting duct (CCD) in the kidney nephron. Under the regulation of the steroid hormone aldosterone, ENaC is a major determinant of sodium (Na(+) ) and water balance. The ability of aldosterone to regulate microRNAs (miRs) in the kidney has recently been realized, but the role of miRs in Na(+) regulation has not been well established. Here we demonstrate that expression of a miR cluster mmu-miR-23∼24∼27, is upregulated in the CCD by aldosterone stimulation both in vitro and in vivo...
September 16, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27633993/notch-signaling-promotes-nephrogenesis-by-downregulating-six2
#18
Eunah Chung, Patrick Deacon, Sierra Marable, Juhyun Shin, Joo-Seop Park
During nephrogenesis, multipotent mesenchymal nephron progenitors develop into distinct epithelial segments. Each nephron segment has distinct cell types and physiological function. In the current model of kidney development, Notch signaling promotes the formation of proximal tubules and represses the formation of distal tubules. Here, we present a novel role of Notch in nephrogenesis. We show in mice that differentiation of nephron progenitors requires downregulation of Six2, a transcription factor required for progenitor maintenance, and that Notch signaling is necessary and sufficient for Six2 downregulation...
November 1, 2016: Development
https://www.readbyqxmd.com/read/27600292/a-low-salt-diet-increases-the-expression-of-renal-sirtuin-1-through-activation-of-the-ghrelin-receptor-in-rats
#19
Shao-Yu Yang, Shuei-Liong Lin, Yung-Ming Chen, Vin-Cent Wu, Wei-Shiung Yang, Kwan-Dun Wu
Previous studies have shown that sirtuin 1 (Sirt1) is renoprotective; however, details regarding its distribution and functions in the kidney remain unknown. Here, we demonstrated that Sirt1 was mainly expressed in the tubulointerstitial cells of normal rat kidneys and was co-localized with aquaporin 2, indicating it may be involved in water/salt regulation. Renal Sirt1 expression increased in the non-glomerular cytoplasmic portion of the kidney after a 24-h fast, but no significant changes in Sirt1 expression occurred after water loading (50 mL/kg) or 24-h water deprivation...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27598420/water-balance-and-salt-wasting-in-the-first-year-of-life-the-role-of-aldosterone-signaling-defects
#20
Carla Bizzarri, Stefania Pedicelli, Marco Cappa, Stefano Cianfarani
In newborns and infants, dehydration and salt wasting represent a relatively common cause of admission to hospital and may result in life-threatening complications. Kidneys are responsible for electrolyte homoeostasis, but neonatal kidneys show low glomerular filtration rate and immaturity of the distal nephron, leading to reduced ability to concentrate urine. High extrarenal fluid losses often contribute to the increased occurrence of electrolyte disorders. Aldosterone is essential for sodium retention in the kidney, salivary glands, sweat glands and colon...
September 7, 2016: Hormone Research in Pædiatrics
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