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Vitamin D AND klotho

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https://www.readbyqxmd.com/read/27879395/a-computationally-identified-compound-antagonizes-excess-fgf-23-signaling-in-renal-tubules-and-a-mouse-model-of-hypophosphatemia
#1
Zhousheng Xiao, Demian Riccardi, Hector A Velazquez, Ai L Chin, Charles R Yates, Jesse D Carrick, Jeremy C Smith, Jerome Baudry, L Darryl Quarles
Fibroblast growth factor-23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. Using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23-induced activation of the FGFR/α-KL complex...
November 22, 2016: Science Signaling
https://www.readbyqxmd.com/read/27818277/comparison-of-the-effects-of-novel-vitamin-d-receptor-analog-vs-105-and-paricalcitol-on-chronic-kidney-disease-mineral-bone-disorder-in-an-experimental-model-of-chronic-kidney-disease
#2
Hideki Fujii, Yuriko Yonekura, Kentaro Nakai, Keiji Kono, Shunsuke Goto, Shinichi Nishi
When using vitamin D, the most important clinical problems are hypercalcemia, hyperphosphatemia, and vascular calcification. VS-105 is a novel vitamin D receptor (VDR) analog. In the present study, we compared the effects of VS-105 and paricalcitol on chronic kidney disease-mineral bone disorder (CKD-MBD) in a CKD rat model. We used male Sprague-Dawley (SD) rats and performed 5/6 nephrectomy at 8-9 weeks. At 10 weeks, the rats were classified into five groups and administered vehicle, low-dose paricalcitol (LP, 0...
November 3, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27783859/calcium-homeostasis-in-health-and-in-kidney-disease
#3
Sharon M Moe
Calcium is an important ion in cell signaling, hormone regulation, and bone health. Its regulation is complex and intimately connected to that of phosphate homeostasis. Both ions are maintained at appropriate levels to maintain the extracellular to intracellular gradients, allow for mineralization of bone, and to prevent extra skeletal and urinary calcification. The homeostasis involves the target organs intestine, parathyroid glands, kidney, and bone. Multiple hormones converge to regulate the extracellular calcium level: parathyroid hormone, vitamin D (principally 25(OH)D or 1,25(OH)2D), fibroblast growth factor 23, and α-klotho...
September 15, 2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/27721584/the-three-sisters-of-fate-in-multiple-sclerosis-klotho-clotho-fibroblast-growth-factor-23-lachesis-and-vitamin-d-atropos
#4
Hamit Yasar Ellidag, Necat Yilmaz, Fatma Kurtulus, Ozgur Aydin, Esin Eren, Ayca Inci, Suleyman Dolu, Fatma Demet Arslan Ince, Özlem Giray, Aylin Yaman
BACKGROUND: The klotho (Klt)-fibroblast growth factor-23 (FGF-23)-vitamin D axis is the main component of calcium (Ca) and phosphorus (P) metabolisms; on the contrary, it is also secreted from the choroid plexus (CP). PURPOSE: This study is aimed at evaluating serum soluble Klt (sKlt), FGF-23, and 25-(OH)-vitamin D levels in multiple sclerosis (MS) patients. METHODS: Thirty-two relapsing-remitting MS patients (11 males and 21 females; mean age 38...
September 2016: Annals of Neurosciences
https://www.readbyqxmd.com/read/27668003/from-kidneys-govern-bones-to-chronic-kidney-disease-diabetes-mellitus-and-metabolic-bone-disorder-a-crosstalk-between-traditional-chinese-medicine-and-modern-science
#5
REVIEW
Xiao-Qin Wang, Xin-Rong Zou, Yuan Clare Zhang
Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of "Kidneys Govern Bones." Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27622885/fgf23-klotho-signaling-axis-in-the-kidney
#6
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/27576165/klotho-a-humeral-mediator-in-csf-and-plasma-that-influences-longevity-and-susceptibility-to-multiple-complex-disorders-including-depression
#7
REVIEW
M G Pavlatou, A T Remaley, P W Gold
Klotho is a hormone secreted into human cerebrospinal fluid (CSF), plasma and urine that promotes longevity and influences the onset of several premature senescent phenotypes in mice and humans, including atherosclerosis, cardiovascular disease, stroke and osteoporosis. Preliminary studies also suggest that Klotho possesses tumor suppressor properties. Klotho's roles in these phenomena were first suggested by studies demonstrating that a defect in the Klotho gene in mice results in a significant decrease in lifespan...
August 30, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27498418/fgf23-and-parathyroid-hormone-signaling-interact-in-kidney-and-bone
#8
Olena Andrukhova, Carmen Streicher, Ute Zeitz, Reinhold G Erben
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone, suppressing renal phosphate reabsorption and vitamin D hormone synthesis in proximal tubules, and stimulating calcium reabsorption in distal tubules of the kidney. Here, we analyzed the long term sequelae of deficient Fgf23 signaling on bone and mineral metabolism in 9-month-old mice lacking both Fgf23 or Klotho and a functioning vitamin D receptor (VDR). To prevent hypocalcemia in VDR deficient mice, all mice were kept on a rescue diet enriched with calcium, phosphate, and lactose...
November 15, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27496232/design-and-rationale-of-a-multicentre-randomised-double-blind-placebo-controlled-clinical-trial-to-evaluate-the-effect-of-vitamin-d-on-ventricular-remodelling-in-patients-with-anterior-myocardial-infarction-the-vitamin-d-in-acute-myocardial-infarction-vitdami
#9
José Tuñón, Ignacio González-Hernández, Lucía Llanos-Jiménez, Joaquín Alonso-Martín, Juan M Escudier-Villa, Nieves Tarín, Carmen Cristóbal, Petra Sanz, Ana M Pello, Álvaro Aceña, Rocío Carda, Miguel Orejas, Marta Tomás, Paula Beltrán, Marta Calero Rueda, Esther Marcos, José María Serrano-Antolín, Carlos Gutiérrez-Landaluce, Rosa Jiménez, Jorge Cabezudo, Alejandro Curcio, Germán Peces-Barba, Emilio González-Parra, Raquel Muñoz-Siscart, María Luisa González-Casaus, Antonio Lorenzo, Ana Huelmos, Javier Goicolea, Borja Ibáñez, Gonzalo Hernández, Luis M Alonso-Pulpón, Jerónimo Farré, Óscar Lorenzo, Ignacio Mahíllo-Fernández, Jesús Egido
INTRODUCTION: Decreased plasma vitamin D (VD) levels are linked to cardiovascular damage. However, clinical trials have not demonstrated a benefit of VD supplements on left ventricular (LV) remodelling. Anterior ST-elevation acute myocardial infarction (STEMI) is the best human model to study the effect of treatments on LV remodelling. We present a proof-of-concept study that aims to investigate whether VD improves LV remodelling in patients with anterior STEMI. METHODS AND ANALYSIS: The VITamin D in Acute Myocardial Infarction (VITDAMI) trial is a multicentre, randomised, double-blind, placebo-controlled trial...
August 5, 2016: BMJ Open
https://www.readbyqxmd.com/read/27450645/fibroblast-growth-factor-23-and-soluble-klotho-in-patients-with-autosomal-dominant-polycystic-kidney-disease
#10
Kenichi Akiyama, Toshio Mochizuki, Hiroshi Kataoka, Ken Tsuchiya, Kosaku Nitta
AIM: This study aimed to examine the roles of fibroblast growth factor 23 (FGF23) and soluble Klotho in phosphate metabolism in autosomal-dominant polycystic kidney disease (ADPKD) patients. METHODS: We measured these two factors and phosphate metabolism parameters in 80 patients with ADPKD and 53 patients with non-diabetic chronic kidney disease (CKD). RESULTS: The mean serum FGF23 level in the ADPKD group was significantly (2-fold) higher than in the non-diabetic CKD patients, but the mean soluble Klotho level in the ADPKD group was significantly lower in the non-diabetic CKD group...
July 23, 2016: Nephrology
https://www.readbyqxmd.com/read/27403909/-fibroblast-growth-factor-23-in-chronic-kidney-disease-in-children
#11
REVIEW
Magdalena Okarska-Napierała, Piotr Skrzypczyk, Małgorzata Pańczyk-Tomaszewska
Cardiovascular risk in children with chronic kidney disease (CKD) is many times higher compared to their healthy peers, and discovered in year 2000 fibroblast growth factor 23 (FGF23) may be one of the factors responsible. FGF23 together with its cofactor, α-Klotho protein, plays a pivotal role in calcium-phosphorus metabolism in patients with CKD by decreasing secretion of active metabolite of vitamin D and antagonizing phosphate resorption in renal tubules. Studies conducted in recent years revealed that FGF23 directly binds to its receptor on cardiomyocytes and promotes left ventricular hypertrophy...
June 2016: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/27377727/vitamin-d-reactive-oxygen-species-and-calcium-signalling-in-ageing-and-disease
#12
REVIEW
Michael J Berridge
Vitamin D is a hormone that maintains healthy cells. It functions by regulating the low resting levels of cell signalling components such as Ca(2+) and reactive oxygen species (ROS). Its role in maintaining phenotypic stability of these signalling pathways depends on the ability of vitamin D to control the expression of those components that act to reduce the levels of both Ca(2+) and ROS. This regulatory role of vitamin D is supported by both Klotho and Nrf2. A decline in the vitamin D/Klotho/Nrf2 regulatory network may enhance the ageing process, and this is well illustrated by the age-related decline in cognition in rats that can be reversed by administering vitamin D...
August 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/27292223/in%C3%A2-vivo-evidence-for-a-limited-role-of-proximal-tubular-klotho-in-renal-phosphate-handling
#13
Noriko Ide, Hannes Olauson, Tadatoshi Sato, Michael Joseph Densmore, Hao Wang, Jun-Ichi Hanai, Tobias E Larsson, Beate Lanske
Klotho is a transmembrane protein expressed in the renal tubules where it acts as a permissive coreceptor for fibroblast growth factor 23 (FGF23). FGF23 signaling reduces the abundance of CYP27b1 and phosphate cotransporters NPT2a and NPT2c, leading to a decrease in 1,25(OH)2D3 synthesis and a rise in urinary phosphate excretion, respectively. Systemic or whole-nephron deletion of Klotho in mice results in renal FGF23 resistance characterized by high 1,25(OH)2D3 and phosphate levels and premature aging. Expression of Klotho is highest in the distal tubules, whereas 25OH vitamin D 1α hydroxylation and phosphate reabsorption predominantly occur in the proximal tubules...
August 2016: Kidney International
https://www.readbyqxmd.com/read/27230843/-bone-disease-in-the-field-of-ckd-mbd
#14
Aiji Yajima, Ken Tsuchiya, Hiroki Yokota, Kosaku Nitta
The pathophysiology and treatment for renal bone disease have made remakable progress. Moreover, osteocyte reseach has made tremendous progress. In the clinical aspect, (1) hyperphosphatemia, (2) hyperparathyroid and hypoparathyroid bone disease in patients with chronic kidney disease, (3) increased serum level of fibroblast growth factor 23 (FGF-23) and(4) reduced level of Klotho should be taken into consideration when analyzing these conditions. On the other hand, hyperphosphatemia must be successfully treated...
June 2016: Clinical Calcium
https://www.readbyqxmd.com/read/27230841/-role-of-parathyroid-hormone-in-klotho-fgf23-system
#15
Takaaki Kimura, Kazuhiro Shiizaki, Makoto Kuro-O
Klotho was originally identified as an anti-aging gene that accelerated aging when disrupted and extended life span when overexpressed in mice. The Klotho gene encodes a single-pass transmembrane protein and is expressed in the kidney and parathyroid gland. Klotho protein functions as an obligate subunit of the receptor for fibroblast growth factor 23 (FGF23). FGF23 is a hormone secreted from osteocytes and osteoblasts and acts on renal tubular cells to promote phosphate excretion into the urine and suppress synthesis of active form of vitamin D (1,25-dihydroxyvitamin D3;1,25(OH)(2)D(3))...
June 2016: Clinical Calcium
https://www.readbyqxmd.com/read/27230836/-pathophysiology-of-primary-hyperparathyroidism
#16
Hiroshi Kaji
Primary hyperparathyroidism is a disease with increased cell proliferation and enhanced PTH secretion due to the escape from negative feedback by calcium ion in parathyroid cells for their tumorization. Involvements of several gene abnormalities have been demonstrated in the pathogenesis of parathyroid tumor. First, an activation of cyclin D1 gene by the translocation of 11 chromosome was found as one of the cause of parathyroid tumorigenesis. Moreover, mutation of multiple endocrine type 1 gene is the most frequent as a genetic cause of sporadic parathyroid tumor...
June 2016: Clinical Calcium
https://www.readbyqxmd.com/read/27219044/multiple-faces-of-fibroblast-growth-factor-23
#17
Xiaobin Han, L Darryl Quarles
PURPOSE OF REVIEW: This review examines the role of fibroblast growth factor-23 (FGF-23) in mineral metabolism, innate immunity and adverse cardiovascular outcomes. RECENT FINDINGS: FGF-23, produced by osteocytes in bone, activates FGFR/α-Klotho (α-Kl) complexes in the kidney. The resulting bone-kidney axis coordinates renal phosphate reabsorption with bone mineralization, and creates a counter-regulatory feedback loop to prevent vitamin D toxicity. FGF-23 acts to counter-regulate the effects of vitamin D on innate immunity and cardiovascular responses...
July 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27215557/klotho-the-holy-grail-of-the-kidney-from-salt-sensitivity-to-chronic-kidney-disease
#18
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/27178987/update-on-fgf23-and-klotho-signaling
#19
Reinhold G Erben
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone known to suppress phosphate reabsorption and vitamin D hormone production in the kidney. Klotho was originally discovered as an anti-aging factor, but the functional role of Klotho is still a controversial issue. Three major functions have been proposed, a hormonal function of soluble Klotho, an enzymatic function as glycosidase, and the function as an obligatory co-receptor for FGF23 signaling. The purpose of this review is to highlight the recent advances in the area of FGF23 and Klotho signaling in the kidney, in the parathyroid gland, in the cardiovascular system, in bone, and in the central nervous system...
September 5, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27134818/systemic-control-of-bone-homeostasis-by-fgf23-signaling
#20
Erica L Clinkenbeard, Kenneth E White
The regulation of phosphate metabolism as an influence on bone homeostasis is profound. Recent advances in understanding the systemic control of Fibroblast growth factor-23 (FGF23) has uncovered novel effectors of endocrine feedback loops for calcium, phosphate, and vitamin D balance that interact with 'traditional' feedback loops for mineral metabolism. Not only are these findings re-shaping research studying phosphate handling and skeletal interactions, they have provided new therapeutic interventions. Emerging data support that the control of FGF23 production in bone and its circulating concentrations is a multi-layered process, with some influences affecting FGF23 transcription and some post-translational modification of the secreted, bioactive protein...
March 1, 2016: Current Molecular Biology Reports
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