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Fgf23-klotho

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https://www.readbyqxmd.com/read/27746322/genetic-diseases-resulting-from-disordered-fgf23-klotho-biology
#1
Michael J Econs, Glenn W Irwin
No abstract text is available yet for this article.
October 13, 2016: Bone
https://www.readbyqxmd.com/read/27659551/-somatotropic-axis-and-molecular-markers-of-mineral-metabolism-in-children-undergoing-chronic-peritoneal-dialysis
#2
María Luisa Ceballos Osorio, Francisco Cano Schuffeneger
: Growth failure is one of the most relevant complications in children with chronic kidney disease (CKD). Among others, growth hormone (GH) resistance and bone mineral disorders have been identified as the most important causes of growth retardation. OBJECTIVES: 1. To characterize bone mineral metabolism and growth hormone bio-markers in CKD children treated with chronic peritoneal dialysis (PD). 2. To evaluate height change with rhGH treatment. PATIENTS AND METHOD: A longitudinal 12-month follow-up in prepuberal PD children...
September 19, 2016: Revista Chilena de Pediatría
https://www.readbyqxmd.com/read/27622885/fgf23-klotho-signaling-axis-in-the-kidney
#3
Reinhold G Erben, Olena Andrukhova
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone protecting against the potentially deleterious effects of hyperphosphatemia by suppression of phosphate reabsorption and of active vitamin D hormone synthesis in the kidney. The kidney is one of the main target organs of FGF23 signaling. The purpose of this review is to highlight the recent advances in the area of FGF23-Klotho signaling in the kidney. During recent years, it has become clear that FGF23 acts independently on proximal and distal tubular epithelium...
September 10, 2016: Bone
https://www.readbyqxmd.com/read/27378183/loss-of-function-of-napiiia-causes-nephrocalcinosis-and-possibly-kidney-insufficiency
#4
Dganit Dinour, Miriam Davidovits, Liat Ganon, Justyna Ruminska, Ian C Forster, Nati Hernando, Eran Eyal, Eli J Holtzman, Carsten A Wagner
BACKGROUND: Inherited metabolic disorders associated with nephrocalcinosis are rare conditions. The aim of this study was to identify the genetic cause of an Israeli-Arab boy from a consanguineous family with severe nephrocalcinosis and kidney insufficiency. METHODS: Clinical and biochemical data of the proband and family members were obtained from both previous and recent medical charts. Genomic DNA was isolated from peripheral blood cells. The coding sequence and splice sites of candidate genes (CYP24A1, CYP27B1, FGF23, KLOTHO, SLC34A3 and SLC34A1) were sequenced directly...
July 4, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/27312441/turning-over-renal-osteodystrophy-dogma-direct-actions-of-fgf23-on-osteoblast-%C3%AE-catenin-pathway
#5
Susan C Schiavi, Rosa M A Moysés
Although recognized as a major complication of chronic kidney disease (CKD), the pathophysiology of the CKD-related mineral and bone disorder (CKD-MBD) is not completely understood. Recently, the inhibition of Wnt/β-catenin pathway in osteocytes by sclerostin has been shown to play a role in CKD-MBD. The study by Carrilo-Lopez et al. confirms this inhibition in an experimental model of CKD. Moreover, they describe direct actions of FGF23-Klotho on osteoblasts, increasing the expression of DKK1, another Wnt/β-catenin pathway inhibitor...
July 2016: Kidney International
https://www.readbyqxmd.com/read/27220755/fibroblast-growth-factor-23-modifies-the-pharmacological-effects-of-angiotensin-receptor-blockade-in-experimental-renal-fibrosis
#6
Maarten A de Jong, Katarina Mirkovic, Rik Mencke, Joost G Hoenderop, René J Bindels, Marc G Vervloet, Jan-Luuk Hillebrands, Jacob van den Born, Gerjan Navis, Martin H de Borst
BACKGROUND: Blockade of the renin-angiotensin-aldosterone system (RAAS) retards progression of chronic kidney disease. Yet, in many patients, the renoprotective effect is incomplete. A high circulating level of the phosphaturic hormone fibroblast growth factor 23 is associated with an impaired response to RAAS blockade-based therapy in clinical studies. Therefore, we addressed whether administration of recombinant fibroblast growth factor 23 (FGF23) interferes with the efficacy of angiotensin receptor blocker (ARB) treatment in a mouse model of renal fibrosis [unilateral ureteral obstruction (UUO)]...
May 24, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/27215557/klotho-the-holy-grail-of-the-kidney-from-salt-sensitivity-to-chronic-kidney-disease
#7
REVIEW
Rigas G Kalaitzidis, Anila Duni, Kostas C Siamopoulos
The Klotho gene displays an extremely shortened life span with loss of function missense mutations leading to premature multiple organ failure, thus resembling human premature aging syndromes. The transmembrane form of Klotho protein functions as an obligatory co-receptor for FGF23. Klotho and FGF23 are crucial components for the regulation of vitamin D metabolism and subsequently blood phosphate levels. The secreted Klotho protein has multiple regulatory functions, including effects on electrolyte homeostasis, on growth factor pathways as well as on oxidative stress, which are currently the object of extensive research...
October 2016: International Urology and Nephrology
https://www.readbyqxmd.com/read/27125741/the-fgf23-klotho-regulatory-network-and-its-roles-in-human-disorders
#8
S Kinoshita, M Kawai
The functions of Klotho (KL) are multifaceted and include the regulation of aging and mineral metabolism. It was originally identified as the gene responsible for premature aging-like symptoms in mice and was subsequently shown to function as a coreceptor in the fibroblast growth factor (FGF) 23 signaling pathway. The discovery of KL as a partner for FGF23 led to significant advances in understanding of the molecular mechanisms underlying phosphate and vitamin D metabolism, and simultaneously clarified the pathogenic roles of the FGF23 signaling pathway in human diseases...
2016: Vitamins and Hormones
https://www.readbyqxmd.com/read/26943611/the-fgf23-klotho-axis-in-the-regulation-of-mineral-and-metabolic-homeostasis
#9
Masanobu Kawai
The function of fibroblast growth factor (FGF) 23 has been suggested to be multifaceted beyond its canonical function as a regulator of mineral metabolism. FGF23 was originally shown to play a central role in phosphate (Pi) and vitamin D metabolism, and a number of diseases associated with dysregulated Pi metabolism have been attributed to abnormal FGF23 signaling activities. The discovery of Klotho as a co-receptor for FGF23 signaling has also accelerated understanding on the molecular mechanisms underlying Pi and vitamin D metabolism...
October 1, 2016: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/26900884/phosphate-and-fgf23-in-the-renoprotective-benefit-of-raas-inhibition
#10
REVIEW
Sophie de Seigneux, Pierre-Yves Martin
Renin angiotensin-aldosterone system (RAAS) blockade is a mainstay of chronic kidney disease (CKD) treatment given its beneficial effects on proteinuria, nephroprotection, heart disease and global mortality. The FGF23/Klotho/phosphate axis is crucial for phosphate excretion. During CKD, loss of Klotho, decreased phosphate excretion and FGF23 elevation are early events contributing both to renal disease progression and to cardiovascular complications. Experimental evidence suggests that Klotho replacement may improve renal and cardiovascular disease during CKD...
April 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/26827953/1-25-dihydroxyvitamin-d-and-klotho-a-tale-of-two-renal-hormones-coming-of-age
#11
Mark R Haussler, G Kerr Whitfield, Carol A Haussler, Marya S Sabir, Zainab Khan, Ruby Sandoval, Peter W Jurutka
1,25-Dihydroxyvitamin D3 (1,25D) is the renal metabolite of vitamin D that signals through binding to the nuclear vitamin D receptor (VDR). The ligand-receptor complex transcriptionally regulates genes encoding factors stimulating calcium and phosphate absorption plus bone remodeling, maintaining a skeleton with reduced risk of age-related osteoporotic fractures. 1,25D/VDR signaling exerts feedback control of Ca/PO4 via regulation of FGF23, klotho, and CYP24A1 to prevent age-related, ectopic calcification, fibrosis, and associated pathologies...
2016: Vitamins and Hormones
https://www.readbyqxmd.com/read/26794822/-phosphorus-a-new-cardiovascular-risk-factor
#12
M Insalaco, R Scuderi, L Zanoli, D Galeano, A Failla, P Fatuzzo, A Granata
Phosphorus is an essential mineral in the regulation of many metabolic processes. However, is known as alterations in serum phosphate levels, compared to the normal range, have clinical relevance: many studies about phosphorus and cardiovascular risk have shown that high serum phosphate levels are associated with clinical and subclinical cardiovascular disease, in CKD and non-CKD patients. In recent years, serum phosphate level within the upper limits of normal range is also identified as a "stealthier killer", and has emerged as a risk factor of cardiovascular mortality and progression of CKD...
November 2015: La Clinica Terapeutica
https://www.readbyqxmd.com/read/26764419/the-effect-of-gh-treatment-on-serum-fgf23-and-klotho-in-gh-deficient-children
#13
Alexandra Efthymiadou, Dimitra Kritikou, Stefanos Mantagos, Dionisios Chrysis
BACKGROUND: Normal phosphate homeostasis is essential for normal linear growth. The phosphaturic fibroblast growth factor 23 (FGF23)/Klotho axis is a major regulator of phosphate homeostasis; therefore, an intact FGF23/Klotho axis is important for normal linear growth. On the other hand, GH/IGF1 axis has opposing effects on phosphate homeostasis, but the underline mechanisms remain unclear. AIM: The main objective of this study was to investigate the possible interactions of FGF23 and its co-receptor Klotho, with growth hormone (GH)/IGF1 axis in the regulation of phosphate metabolism in GH-deficient children under GH treatment...
April 2016: European Journal of Endocrinology
https://www.readbyqxmd.com/read/26381618/fluoride-modulates-parathyroid-hormone-secretion-in-vivo-and-in-vitro
#14
Chaitanya P Puranik, Kathleen A Ryan, Zhaoyu Yin, E Angeles Martinez-Mier, John S Preisser, Eric T Everett
The study objective was to investigate the effects of fluoride on intact parathyroid hormone (iPTH) secretion. Thyro-parathyroid complexes (TPC) from C3H (n = 18) and B6 (n = 18) mice were cultured in Ca²⁺-optimized medium. TPC were treated with 0, 250, or 500 µM NaF for 24 h and secreted iPTH assayed by ELISA. C3H (n = 78) and B6 (n = 78) mice were gavaged once with distilled or fluoride (0.001 mg [F⁻]/g of body weight) water. At serial time points (0.5-96 h) serum iPTH, fluoride, total calcium, phosphorus, and magnesium levels were determined...
2015: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/26347327/significant-roles-of-anti-aging-protein-klotho-and-fibroblast-growth-factor23-in-cardiovascular-disease
#15
REVIEW
Hong-Ying Ding, Hou-Xun Ma
The klotho gene has been identified as an aging suppressor that encodes a protein involved in cardiovascular disease (CVD). The inactivation of the klotho gene causes serious systemic disorders resembling human aging, such as atherosclerosis, diffuse vascular calcification and shortened life span. Klotho has been demonstrated to ameliorate vascular endothelial dysfunction and delay vascular calcification. Furthermore, klotho gene polymorphisms in the human are associated with various cardiovascular events. Recent experiments show that klotho may reduce transient receptor potential canonical6 (TRPC6) channels, resulting in protecting the heart from hypertrophy and systolic dysfunction...
July 2015: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/26307633/acetazolamide-sensitive-tissue-calcification-and-aging-of-klotho-hypomorphic-mice
#16
Christina B Leibrock, Ioana Alesutan, Jakob Voelkl, Diana Michael, Tatsiana Castor, Ursula Kohlhofer, Leticia Quintanilla-Martinez, Laura Kübler, Julia G Mannheim, Bernd J Pichler, Kevin P Rosenblatt, Makoto Kuro-o, Florian Lang
UNLABELLED: Klotho, a protein expressed mainly in the kidney, is required for the inhibitory effect of FGF23 on renal 1,25(OH)2D3 formation. Klotho counteracts vascular calcification and diverse age-related disorders. Klotho-hypomorphic mice (kl/kl) suffer from severe vascular calcification and rapid aging. The calcification is at least in part caused by excessive 1,25(OH)2D3, Ca(2+), and phosphate concentrations in blood, which trigger osteogenic signaling including upregulation of alkaline phosphatase (Alpl)...
January 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/26303319/pathophysiology-of-calcium-phosphorus-and-magnesium-dysregulation-in-chronic-kidney-disease
#17
REVIEW
Arnold J Felsenfeld, Barton S Levine, Mariano Rodriguez
Calcium, phosphorus, and magnesium homeostasis is altered in chronic kidney disease (CKD). Hypocalcemia, hyperphosphatemia, and hypermagnesemia are not seen until advanced CKD because adaptations develop. Increased parathyroid hormone (PTH) secretion maintains serum calcium normal by increasing calcium efflux from bone, renal calcium reabsorption, and phosphate excretion. Similarly, renal phosphate excretion in CKD is maintained by increased secretion of fibroblast growth factor 23 (FGF23) and PTH. However, the phosphaturic effect of FGF23 is reduced by downregulation of its cofactor Klotho necessary for binding FGF23 to FGF receptors...
November 2015: Seminars in Dialysis
https://www.readbyqxmd.com/read/26298739/soluble-klotho-and-mortality-the-ludwigshafen-risk-and-cardiovascular-health-study
#18
Vincent M Brandenburg, Marcus E Kleber, Marc G Vervloet, Tobias E Larsson, Andreas Tomaschitz, Stefan Pilz, Tatjana Stojakovic, Graciela Delgado, Tanja B Grammer, Nikolaus Marx, Winfried März, Hubert Scharnagl
BACKGROUND: Experimental evidence suggests that soluble klotho (s-klotho), a co-receptor for fibroblast growth factor 23 (FGF23), may modulate cardiovascular risk through multiple mechanisms. However, the predictive value of s-klotho in patients remains unclear. Therefore, the present study examined in a large cohort of patients referred for coronary angiography whether s-klotho is associated with cardiovascular and total mortality. METHODS: The longitudinal associations between baseline s-klotho and FGF23 concentrations and mortality were evaluated in 2948 participants of the Ludwigshafen Risk and Cardiovascular Health Study (LURIC), referred for coronary angiography...
October 2015: Atherosclerosis
https://www.readbyqxmd.com/read/26287968/xeno-klotho-inhibits-parathyroid-hormone-signaling
#19
Tsuneo Takenaka, Tsutomu Inoue, Takashi Miyazaki, Matsuhiko Hayashi, Hiromichi Suzuki
Although fibroblast growth factor (FGF) 23 was recently identified as a phosphatonin that influences vitamin D metabolism, the underlying signaling mechanisms remain unclear. FGF23 elevates the renal levels of membrane-associated klotho as well as soluble klotho. Klotho is expressed on distal tubules. Upon enzymatic cleavage, soluble klotho is released into the renal interstitial space and then into the systemic circulation. The expression of 25-hydroxyvitamin D3 1α-hydroxylase (1-OH) on proximal tubular cells is controlled by parathyroid hormone (PTH)...
February 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/26279337/gender-specific-association-between-serum-fibroblast-growth-factor-23-%C3%AE-klotho-and-coronary-artery-and-aortic-valve-calcification
#20
Hideaki Morita, Yoshihiro Takeda, Shu-ichi Fujita, Yusuke Okamoto, Kazushi Sakane, Kunihiro Teramoto, Michishige Ozeki, Ryunosuke Tasaki, Shun Kizawa, Koichi Sohmiya, Masaaki Hoshiga, Nobukazu Ishizaka
AIM: Fibroblast growth factor 23 (FGF23) and α-Klotho have been recently identified to play a crucial role in calcium/phosphate metabolism. We herein investigated the possible relation between serum FGF23/α-Klotho levels and coronary artery calcification (CAC) and aortic valve calcification (AVC). METHODS: Among subjects with diagnosed or suspected coronary artery disease (CAD), CAC and AVC were estimated via the Agatston score of 320-detector computed tomography images, and serum FGF23 and α-Klotho levels were measured...
2015: Journal of Atherosclerosis and Thrombosis
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