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https://www.readbyqxmd.com/read/29145399/point-mutation-in-d8c-domain-of-tamm-horsfall-protein-uromodulin-in-transgenic-mice-causes-progressive-renal-damage-and-hyperuricemia
#1
Lijie Ma, Yan Liu, Nichole K Landry, Tarek M El-Achkar, John C Lieske, Xue-Ru Wu
Hereditary mutations in Tamm-Horsfall protein (THP/uromodulin) gene cause autosomal dominant kidney diseases characterized by juvenile-onset hyperuricemia, gout and progressive kidney failure, although the disease pathogenesis remains unclear. Here we show that targeted expression in transgenic mice of a mutation within the domain of 8 cysteines of THP in kidneys' thick ascending limb (TAL) caused unfolded protein response in younger (1-month old) mice and apoptosis in older (12-month old) mice. While the young mice had urine concentration defects and polyuria, such defects progressively reversed in the older mice to marked oliguria, highly concentrated urine, fibrotic kidneys and reduced creatinine clearance...
2017: PloS One
https://www.readbyqxmd.com/read/29122955/dnpep-is-not-the-only-peptidase-that-produces-spak-fragments-in-kidney
#2
Rainelli Koumangoye, Eric Delpire
SPAK (STE20/SPS1-related proline/alanine-rich kinase) regulates Na(+) and Cl(-) reabsorption in the distal convoluted tubule, and possibly in the thick ascending limb of Henle. This kinase phosphorylates and activates the apical Na-Cl cotransporter in the DCT. Western blot analysis reveals that SPAK in kidney exists as a full-length protein as well as shorter fragments that might affect NKCC2 function in the TAL. Recently, we showed that kidney lysates exerts proteolytic activity towards SPAK, resulting in the formation of multiple SPAK fragments with possible inhibitory effects on the kinase...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29100270/albuminuria-confers-renal-resistance-to-loop-diuretics-via-the-stimulation-of-nlrp3-inflammasome-prostaglandin-signaling-in-thick-ascending-limb
#3
Yibo Zhuang, Zhanjun Jia, Caiyu Hu, Guixia Ding, Xintong Zhang, Yue Zhang, Guangrui Yang, Rajeev Rohatgi, Songming Huang, John Ci-Jiang He, Aihua Zhang
Renal resistance to loop diuretics is a frequent complication in a number of kidney disease patients with elusive mechanism. Employing human renal biopsy specimens, albumin overload mouse model, and primary cultures of mouse renal tubular cells, albuminuria effect on NKCC2 expression and function and the underlying mechanisms were investigated. In the renal biopsy specimens of albuminuric patients, we found that NKCC2 was significantly downregulated with a negative correlation with albuminuria severity as examined by immunohistochemistry...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29046296/geraniin-is-a-diuretic-by-inhibiting-the-na-k-2cl-cotransporter-nkcc2
#4
Erika Moreno, Juan A Gayosso, Jose Ramón Montejano, Georgina Almaguer, Norma Vázquez, Cristino Cruz, Adriana Mercado, Norma A Bobadilla, Gerardo Gamba, Alfredo Sierra, Victoria Ramírez
Geranium seemannii Peyr is a perennial plant endemic in central Mexico that has been widely used for its diuretic effect, but the responsible compound of this effect is unknown as well as the mechanism by which the diuretic effect is achieved. Geraniin is one of the compounds isolated from this kind of geranium. This study was designed to determinate whether geraniin possesses diuretic activity and to elucidate the mechanism of action. Geraniin was extracted and purified from Geranium seemannii Peyr. Male Wistar rats were divided into four groups: 1) Control, 2) 75 mg/kg of geraniin, 3) 20 mg/Kg of furosemide, and 4) 10 mg/Kg of hydrochlorothiazide...
October 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28951728/urinary-exosomes-and-their-cargo-potential-biomarkers-for-mineralocorticoid-arterial-hypertension
#5
REVIEW
Eric R Barros, Cristian A Carvajal
Arterial hypertension (AHT) currently affects approximately 40% of adults worldwide, and its pathological mechanisms are mainly related to renal, vascular, and endocrine systems. Steroid hormones as aldosterone and cortisol are highly relevant to human endocrine physiology, and also to endocrine hypertension. Pathophysiological conditions, such as primary aldosteronism, affect approximately 10% of patients diagnosed with AHT and are secondary to a high production of aldosterone, increasing the risk also for cardiovascular damage and heart diseases...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28940314/dietary-sodium-induces-a-redistribution-of-the-tubular-metabolic-workload
#6
Khalil Udwan, Ahmed Abed, Isabelle Roth, Eva Dizin, Marc Maillard, Carla Bettoni, Johannes Loffing, Carsten A Wagner, Aurélie Edwards, Eric Feraille
KEY POINTS: Body Na(+) content is tightly controlled by regulated urinary Na(+) excretion. The intrarenal mechanisms mediating adaptation to variations in dietary Na(+) intake are incompletely characterized. We confirmed and expanded observations in mice that variations in dietary Na(+) intake do not alter the glomerular filtration rate but alter the total and cell-surface expression of major Na(+) transporters all along the kidney tubule. Low dietary Na(+) intake increased Na(+) reabsorption in the proximal tubule and decreased it in more distal kidney tubule segments...
November 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28877879/uninephrectomy-and-apical-fluid-shear-stress-decrease-enac-abundance-in-collecting-duct-principal-cells
#7
Thomas Ernandez, Khalil Udwan, Alexandra Chassot, Pierre-Yves Martin, Eric Feraille
Acute nephron reduction such as after living kidney donation may increase the risk of hypertension. Uninephrectomy induces major hemodynamic changes in the remaining kidney resulting in rapid increase of single nephron GFR and fluid delivery in the distal nephron. Decreased sodium (Na) fractional reabsorption after the distal tubule has been reported after uninephrectomy in animals preserving volume homeostasis. In the present study, we thought to specifically explore the effect of unilateral nephrectomy on ENaC subunits expression in mice...
September 6, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28835421/effect-of-salt-intake-on-afferent-arteriolar-dilatation-role-of-connecting-tubule-glomerular-feedback-ctgf
#8
Hong Wang, Cesar A Romero, J X Masjoan Juncos, Sumit R Monu, Edward L Peterson, Oscar A Carretero
Afferent arteriole (Af-Art) resistance is modulated by 2 intrinsic nephron feedbacks: 1) vasoconstrictor tubuloglomerular feedback (TGF), which is mediated by NKCC2 in the macula densa and blocked by furosemide; and 2) vasodilator connecting tubule glomerular feedback (CTGF), which is mediated by ENaC in the connecting tubule and blocked by benzamil. High salt intake reduces the Af-Art vasoconstrictor ability in Dahl salt-sensitive rats (Dahl SS). Previously, we measured CTGF indirectly using the differences between the TGF responses with and without CTGF inhibition...
August 23, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28760814/a-sall1-nurd-interaction-regulates-multipotent-nephron-progenitors-and-is-required-for-loop-of-henle-formation
#9
Jeannine M Basta, Lynn Robbins, Darcy R Denner, Grant R Kolar, Michael Rauchman
The formation of the proper number of nephrons requires a tightly regulated balance between renal progenitor cell self-renewal and differentiation. The molecular pathways that regulate the transition from renal progenitor to renal vesicle are not well understood. Here, we show that Sall1interacts with the nucleosome remodeling and deacetylase complex (NuRD) to inhibit premature differentiation of nephron progenitor cells. Disruption of Sall1-NuRD in vivo in knock-in mice (ΔSRM) resulted in accelerated differentiation of nephron progenitors and bilateral renal hypoplasia...
September 1, 2017: Development
https://www.readbyqxmd.com/read/28688582/net-k-secretion-in-the-thick-ascending-limb-of-mice-on-a-low-na-high-k-diet
#10
Bangchen Wang, Donghai Wen, Huaqing Li, Jun Wang-France, Steven C Sansom
Because of its cardio-protective effects, a low-Na, high-K diet (LNaHK) is often warranted in conjunction with diuretics to treat hypertensive patients. However, it is necessary to understand the renal handling of such diets in order to choose the best diuretic. Wild-type (WT) or Renal Outer Medullary K channel (ROMK) knockout mice (KO) were given a regular (CTRL), LNaHK, or high-K diet (HK) for 4-7 days. On LNaHK, mice treated with either IP furosemide for 12 hrs, or given furosemide in drinking water for 7 days, exhibited decreased K clearance...
October 2017: Kidney International
https://www.readbyqxmd.com/read/28678861/ecstasy-induces-reactive-oxygen-species-kidney-water-absorption-and-rhabdomyolysis-in-normal-rats-effect-of-n-acetylcysteine-and-allopurinol-in-oxidative-stress-and-muscle-fiber-damage
#11
Ana C de Bragança, Regina L M Moreau, Thales de Brito, Maria H M Shimizu, Daniele Canale, Denise A de Jesus, Ana M G Silva, Pedro H Gois, Antonio C Seguro, Antonio J Magaldi
BACKGROUND: Ecstasy (Ec) use produces hyperthermia, excessive sweating, intense thirst, an inappropriate antidiuretic hormone secretion (SIADH) and a multisystemic toxicity due to oxidative stress (OS). Intense thirst induces high intake of pure water, which associated with SIADH, usually develops into acute hyponatremia (Hn). As Hn is induced rapidly, experiments to check if Ec acted directly on the Inner Medullary Collecting Ducts (IMCD) of rats were conducted. Rhabdomyolysis and OS were also studied because Ec is known to induce Reactive Oxygen Species (ROS) and tissue damage...
2017: PloS One
https://www.readbyqxmd.com/read/28662032/renal-localization-and-regulation-by-dietary-phosphate-of-the-mct14-orphan-transporter
#12
Thomas Knöpfel, Alexander Atanassoff, Nati Hernando, Jürg Biber, Carsten A Wagner
MCT14 is an orphan transporter belonging to the SLC16 transporter family mediating the transport of monocarboxylates, aromatic amino acids, creatine, and thyroid hormones. The expression, tissue localization, regulation, and function of MCT14 are unknown. In mouse MCT14 mRNA abundance is highest in kidney. Using a newly developed and validated antibody, MCT14 was localized to the luminal membrane of the thick ascending limb of the loop of Henle colocalizing in the same cells with uromodulin and NKCC2. MCT14 mRNA and protein was found to be highly regulated by dietary phosphate intake in mice being increased by high dietary phosphate intake at both mRNA and protein level...
2017: PloS One
https://www.readbyqxmd.com/read/28614115/trafficking-and-regulation-of-the-nkcc2-cotransporter-in-the-thick-ascending-limb
#13
Kerim Mutig
PURPOSE OF REVIEW: The kidney Na-K-2Cl cotransporter (NKCC2) is essential for urinary concentration and renal electrolyte handling. Loss of function mutations in the NKCC2 gene cause urinary salt and potassium wasting, whereas excessive NKCC2 function has been linked to high blood pressure. Loop diuretics, targeting the transporter, are instrumental for relieving edema or hypertension. This review focuses on intrinsic mechanisms regulating NKCC2 activity at the posttranslational level, namely its trafficking and phosphorylation...
September 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28607127/role-of-the-primary-cilia-on-the-macula-densa-and-thick-ascending-limbs-in-regulation-of-sodium-excretion-and-hemodynamics
#14
Jiangping Song, Lei Wang, Fan Fan, Jin Wei, Jie Zhang, Yan Lu, Yiling Fu, Shaohui Wang, Luis A Juncos, Ruisheng Liu
We investigated the significance of the primary cilia on the macula densa and thick ascending limb (TAL) in regulation of renal hemodynamics, sodium excretion, and blood pressure in this study. A tissue-specific primary cilia knock-out (KO) mouse line was generated by crossing NKCC2-Cre mice with IFT88-Δ/flox mice (NKCC2(CRE); IFT88Δ(/flox)), in which the primary cilia were deleted from the macula densa and TAL. NO generation was measured with a fluorescent dye (4,5-diaminofluorescein diacetate) in isolated perfused juxtaglomerular apparatus...
August 2017: Hypertension
https://www.readbyqxmd.com/read/28577072/regulation-of-renal-na-k-cl-cotransporters-by-vasopressin
#15
REVIEW
Sebastian Bachmann, Kerim Mutig
Vasopressin (AVP) induces antidiuresis, thus playing an essential role in body water and electrolyte homeostasis. Its antidiuretic effects are mediated chiefly by V2 vasopressin receptors (V2R) expressed along the distal nephron and collecting duct epithelia. NaCl reabsorption in the distal nephron, which includes the thick ascending limb (TAL) and distal convoluted tubule (DCT), largely depends on the activity of two structurally related Na-(K)-Cl cotransporters, NKCC2 in TAL and NCC in DCT. AVP-induced activation of these transporters contributes to urine concentration and renal electrolyte reabsorption...
August 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28515172/cross-sex-transplantation-alters-gene-expression-and-enhances-inflammatory-response-in-the-transplanted-kidneys
#16
COMPARATIVE STUDY
Lei Wang, Jiangping Song, Shaohui Wang, Jacentha Buggs, Rongjun Chen, Jie Zhang, Liqing Wang, Song Rong, Wenbin Li, Jin Wei, Ruisheng Liu
Kidney transplantation (KTX) is a life-saving procedure for patients with end-stage renal disease. Expression levels of many genes in the kidney vary between males and females, which may play an essential role in the sex differences in graft function. However, whether these differences are affected after cross-sex-KTX is unknown. In the present study, we assessed postoperative changes in genotype, function, and inflammatory responses of the grafts in same-sex- and cross-sex-KTX. Single kidney transplants were performed between same and different sex C57BL/6 mice paired into four combination groups: female donor/female recipient (F/F); male donor/male recipient (M/M); female donor/male recipient (F/M); and male donor/female recipient (M/F)...
August 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28507171/first-in-man-demonstration-of-direct-endothelin-mediated-natriuresis-and-diuresis
#17
RANDOMIZED CONTROLLED TRIAL
Robert W Hunter, Rebecca Moorhouse, Tariq E Farrah, Iain M MacIntyre, Takae Asai, Peter J Gallacher, Debbie Kerr, Vanessa Melville, Alicja Czopek, Emma E Morrison, Jess R Ivy, James W Dear, Matthew A Bailey, Jane Goddard, David J Webb, Neeraj Dhaun
Endothelin (ET) receptor antagonists are potentially novel therapeutic agents in chronic kidney disease and resistant hypertension, but their use is complicated by sodium and water retention. In animal studies, this side effect arises from ETB receptor blockade in the renal tubule. Previous attempts to determine whether this mechanism operates in humans have been confounded by the hemodynamic consequences of ET receptor stimulation/blockade. We aimed to determine the effects of ET signaling on salt transport in the human nephron by administering subpressor doses of the ET-1 precursor, big ET-1...
July 2017: Hypertension
https://www.readbyqxmd.com/read/28331059/adaptive-changes-in-gfr-tubular-morphology-and-transport-in-subtotal-nephrectomized-kidneys-modeling-and-analysis
#18
Anita T Layton, Aurélie Edwards, Volker Vallon
Removal of renal mass stimulates anatomical and functional adaptations in the surviving nephrons, including elevations 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...
August 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28274925/salt-supplementation-ameliorates-developmental-kidney-defects-in-cox-2-mice
#19
Patrick Slattery, Stefanie Frölich, Itamar Goren, Rolf M Nüsing
Deficiency of cyclooxygenase-2 (COX-2) activity in the early postnatal period causes impairment of kidney development leading to kidney insufficiency. We hypothesize that impaired NaCl reabsorption during the first days of life is a substantial cause for nephrogenic defects observed in COX-2(-/-) mice and that salt supplementation corrects these defects. Daily injections of NaCl (0.8 mg·g(-1)·day(-1)) for the first 10 days after birth ameliorated impaired kidney development in COX-2(-/-) pups resulting in an increase in glomerular size and fewer immature superficial glomeruli...
June 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28253301/targeting-gene-expression-to-specific-cells-of-kidney-tubules-in-vivo-using-adenoviral-promoter-fragments
#20
Sumiyo Watanabe, Toru Ogasawara, Yoshifuru Tamura, Taku Saito, Toshiyuki Ikeda, Nobuchika Suzuki, Tatsuo Shimosawa, Shigeru Shibata, Ung-Il Chung, Masaomi Nangaku, Shunya Uchida
Although techniques for cell-specific gene expression via viral transfer have advanced, many challenges (e.g., viral vector design, transduction of genes into specific target cells) still remain. We investigated a novel, simple methodology for using adenovirus transfer to target specific cells of the kidney tubules for the expression of exogenous proteins. We selected genes encoding sodium-dependent phosphate transporter type 2a (NPT2a) in the proximal tubule, sodium-potassium-2-chloride cotransporter (NKCC2) in the thick ascending limb of Henle (TALH), and aquaporin 2 (AQP2) in the collecting duct...
2017: PloS One
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