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https://www.readbyqxmd.com/read/28919046/fgf23-activates-injury-primed-renal-fibroblasts-via-fgfr4-dependent-signalling-and-enhancement-of-tgf-%C3%AE-autoinduction
#1
Edward R Smith, Stephen G Holt, Tim D Hewitson
Bone-derived fibroblast growth factor 23 (FGF23) is an important endocrine regulator of mineral homeostasis with effects transduced by cognate FGF receptor (FGFR)1-α-Klotho complexes. Circulating FGF23 levels rise precipitously in patients with kidney disease and portend to worse renal and cardiovascular outcomes. De novo expression of FGF23 has been found in the heart and kidney following injury but its significance remains unclear. Studies showing that exposure to chronically high FGF23 concentrations activates hypertrophic gene programmes in the cardiomyocyte, has spawned intense interest in other pathological off-target effects of FGF23 excess...
September 14, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28900153/genetic-ablation-of-fgf23-or-klotho-does-not-modulate-experimental-heart-hypertrophy-induced-by-pressure-overload
#2
Svetlana Slavic, Kristopher Ford, Magalie Modert, Amarela Becirovic, Stephan Handschuh, Andreas Baierl, Nejla Katica, Ute Zeitz, Reinhold G Erben, Olena Andrukhova
Left ventricular hypertrophy (LVH) ultimately leads to heart failure in conditions of increased cardiac pre- or afterload. The bone-derived phosphaturic and sodium-conserving hormone fibroblast growth factor-23 (FGF23) and its co-receptor Klotho have been implicated in the development of uremic LVH. Using transverse aortic constriction (TAC) in gene-targeted mouse models, we examine the role of Fgf23 and Klotho in cardiac hypertrophy and dysfunction induced by pressure overload. TAC profoundly increases serum intact Fgf23 due to increased cardiac and bony Fgf23 transcription and downregulation of Fgf23 cleavage...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877877/acute-blood-loss-stimulates-fibroblast-growth-factor-23-production
#3
Seham Rabadi, Ikemesit Udo, David Evan Leaf, Sushrut Waikar, Marta Christov
Fibroblast growth factor 23 (FGF23) production is upregulated by iron deficiency and hypoxia. However, the influence of acute blood loss, and the resulting increases in circulating erythropoietin, on FGF23 production is unknown. Using wild-type C57BL/6 mice, we show that acute loss of 10% total blood volume leads to an increase in plasma C-terminal FGF23 (cFGF23) levels within six hours, while plasma levels of intact FGF23, phosphate, calcium, parathyroid hormone, iron, and ferritin remain similar to control mice without acute blood loss...
September 6, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28870151/progression-of-arterial-stiffness-is-associated-with-changes-in-bone-mineral-markers-in-advanced-ckd
#4
Rathika Krishnasamy, Sven-Jean Tan, Carmel M Hawley, David W Johnson, Tony Stanton, Kevin Lee, David W Mudge, Scott Campbell, Grahame J Elder, Nigel D Toussaint, Nicole M Isbel
BACKGROUND: Arterial stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease (CKD). There are limited prospective data however on progression of arterial stiffness in CKD, including evaluating associations with bone mineral markers such as fibroblast growth factor 23 (FGF23) and soluble α-klotho (sKl). METHODS: In this prospective, single-center, observational study, arterial stiffness [measured by pulse wave velocity (PWV)] and hormones influencing mineral homeostasis, including serum FGF23 and sKl, were compared between non-dialysis CKD stages 4/5 and healthy controls at baseline and 12 months (12 m)...
September 4, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28867373/etelcalcetide-amg-416-a-peptide-agonist-of-the-calcium-sensing-receptor-preserved-cortical-bone-structure-and-bone-strength-in-subtotal-nephrectomized-rats-with-established-secondary-hyperparathyroidism
#5
Xiaodong Li, Longchuan Yu, Frank Asuncion, Mario Grisanti, Shawn Alexander, Kelly Hensley, Chun-Ya Han, Qing-Tian Niu, Denise Dwyer, Kelly Villasenor, Marina Stolina, Charles Dean, Michael S Ominsky, Hua Zhu Ke, James E Tomlinson, William G Richards
Sustained elevation of parathyroid hormone (PTH) is catabolic to cortical bone, as evidenced by deterioration in bone structure (cortical porosity), and is a major factor for increased fracture risk in chronic kidney disease (CKD). Etelcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces PTH levels in subtotal nephrectomized (Nx) rats and in hemodialysis patients with secondary hyperparathyroidism (SHPT) in clinical studies; however, effects of etelcalcetide on bone have not been determined...
September 1, 2017: Bone
https://www.readbyqxmd.com/read/28860784/effect-of-additive-calcium-administration-on-fgf23-levels-in-patients-with-mild-chronic-kidney-disease-treated-with-calcitriol-a-randomized-open-labeled-clinical-trial
#6
Nayoung Han, Su Hyun Hong, Yon Su Kim, Dong Ki Kim, In-Wha Kim, Eunhee Ji, Jung Mi Oh
BACKGROUND: The purpose of the present study was to determine the effect of additional calcium carbonate treatment on fibroblast growth factor 23 (FGF23) levels in patients treated with calcitriol. METHODS: In this randomized, open-labeled, and parallel-group study, a total of 30 patients with early chronic kidney disease (CKD) and vitamin D deficiency were randomly assigned to two groups and received interventions for 8 weeks: 1) a combination of calcium carbonate and calcitriol group; and 2) calcitriol only group...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28859264/adefovir-induced-fanconi-syndrome-associated-with-osteomalacia
#7
Samel Park, Woo-Il Kim, Dai-Hyun Cho, Yeo-Joo Kim, Hong-Soo Kim, Ji-Hee Kim, Seung-Kuy Cha, Kyu-Sang Park, Ji-Hye Lee, Sang Mi Lee, Eun Young Lee
Fanconi syndrome is a dysfunction of the proximal renal tubules that results in impaired reabsorption and increased urinary loss of phosphate and other solutes. The pathophysiology of drug-induced Fanconi syndrome is unclear. Here we report the case of a 36-year-old woman who presented with pain in multiple bones and proteinuria. She had a 7-year history of taking adefovir at 10 mg/day for chronic hepatitis B. Three years previously she had received surgery for a nontraumatic right femur neck fracture, after which she continued to complain of pain in multiple bones, and proteinuria, glycosuria, and phosphaturia were noted...
September 1, 2017: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/28858396/histopathological-and-genetic-review-of-phosphaturic-mesenchymal-tumours-mixed-connective-tissue-variant
#8
Yuichi Yamada, Izumi Kinoshita, Kenichi Kohashi, Hidetaka Yamamoto, Takeshi Iwasaki, Hiroshi Otsuka, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yuki Kuma, Nokitaka Setsu, Yuki Koga, Yumi Honda, Takeshi Inoue, Hiroyuki Yanai, Kyoko Yamashita, Ichiro Ito, Mitsuru Takahashi, Shouichi Ohga, Masutaka Furue, Yasuharu Nakashima, Yoshinao Oda
AIMS: Phosphaturic mesenchymal tumour, mixed connective tissue variant (PMT-MCT), is a tumour of uncertain differentiation, characterised by 'smudgy/grungy' calcification and vitamin D-resistant phosphaturic osteomalacia. FGF23 is recognised as a reliable marker of PMT-MCT, but quantitative evaluation of it has never been performed. We reviewed cases of tumour-associated osteomalacia or histologically definitive PMT-MCT without osteomalacia using histological, immunohistochemical and genetic methods and evaluated the diagnostic significance of these findings...
August 31, 2017: Histopathology
https://www.readbyqxmd.com/read/28844316/identifying-early-pathogenic-events-during-vascular-calcification-in-uremic-rats
#9
Luis Hortells, Cecilia Sosa, Natalia Guillén, Susana Lucea, Ángel Millán, Víctor Sorribas
Vascular calcification in chronic kidney disease is a very complex process traditionally explained in multifactorial terms. Here we sought to clarify relevance of the diverse agents acting on vascular calcification in uremic rats and distinguish between initiating and complicating factors. After 5/6 nephrectomy, rats were fed a 1.2% phosphorus diet and analyzed at different time points. The earliest changes observed in the aortic wall were noticed 11 weeks after nephrectomy: increased Wnt inhibitor Dkk1 mRNA expression and tissue non-specific alkaline phosphatase (TNAP) expression and activity...
August 23, 2017: Kidney International
https://www.readbyqxmd.com/read/28843411/the-activin-receptor-is-stimulated-in-the-skeleton-vasculature-heart-and-kidney-during-chronic-kidney-disease
#10
Matthew J Williams, Toshifumi Sugatani, Olga A Agapova, Yifu Fang, Joseph P Gaut, Marie-Claude Faugere, Hartmut H Malluche, Keith A Hruska
We examined activin receptor type IIA (ActRIIA) activation in chronic kidney disease (CKD) by signal analysis and inhibition in mice with Alport syndrome using the ActRIIA ligand trap RAP-011 initiated in 75-day-old Alport mice. At 200 days of age, there was severe CKD and associated Mineral and Bone Disorder (CKD-MBD), consisting of osteodystrophy, vascular calcification, cardiac hypertrophy, hyperphosphatemia, hyperparathyroidism, elevated FGF23, and reduced klotho. The CKD-induced bone resorption and osteoblast dysfunction was reversed, and bone formation was increased by RAP-011...
August 23, 2017: Kidney International
https://www.readbyqxmd.com/read/28838895/associations-of-fibroblast-growth-factor-23-vitamin-d-and-parathyroid-hormone-with-5-year-outcomes-in-a-prospective-primary-care-cohort-of-people-with-chronic-kidney-disease-stage-3
#11
Adam Shardlow, Natasha J McIntyre, Richard J Fluck, Christopher W McIntyre, Maarten W Taal
OBJECTIVES: Vitamin D deficiency, elevated fibroblast growth factor 23 (FGF23) and elevated parathyroid hormone (PTH) have each been associated with increased mortality in people with chronic kidney disease (CKD). Previous studies have focused on the effects of FGF23 in relatively advanced CKD. This study aims to assess whether FGF23 is similarly a risk factor in people with early CKD, and how this risk compares to that associated with vitamin D deficiency or elevated PTH. DESIGN: Prospective cohort study...
August 23, 2017: BMJ Open
https://www.readbyqxmd.com/read/28834363/decreased-expression-of-thrombomodulin-in-endothelial-cells-by-fibroblast-growth-factor-23-%C3%AE-klotho
#12
Kenji Tanaka, Tancharoen Salunya, Yoshihiro Motomiya, Yasuki Motomiya, Yoko Oyama, Munekazu Yamakuchi, Ikuro Maruyama
Chronic kidney disease (CKD) has been known to be a state of excessive fibroblast growth factor-23 (FGF23) and α-Klotho deficiency. Patients undergoing hemodialysis have an increased mortality risk associated with cardiovascular disease and endothelial dysfunction. The mechanism responsible for the relationship of FGF23 to endothelial damage in these patients has been unclear. On the other hands, increasing evidences have demonstrated that thrombomodulin (TM) plays an important role in the endothelial barrier...
August 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/28815282/correction-of-vitamin-d-status-by-calcidiol-pharmacokinetic-profile-safety-and-biochemical-effects-on-bone-and-mineral-metabolism-of-daily-and-weekly-dosage-regimens
#13
S Minisola, L Cianferotti, P Biondi, C Cipriani, C Fossi, F Franceschelli, F Giusti, G Leoncini, J Pepe, H A Bischoff-Ferrari, M L Brandi
RATIONALE: Calcidiol can be employed to correct vitamin D deficiency. MAIN RESULTS: Calcidiol administered at daily and weekly regimens over a period of 3 months was able to successfully raise 25-hydroxyvitamin D levels without altering other markers related to bone and mineral metabolism. SIGNIFICANCE: Calcidiol supplementation is effective and safe. INTRODUCTION: The correction of vitamin D status is necessary to maintain an optimal mineral and skeletal homeostasis...
August 16, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28808057/a-kidney-specific-genetic-control-module-in-mice-governs-endocrine-regulation-of-the-cytochrome-p450-gene-cyp27b1-essential-for-vitamin-d3-activation
#14
Mark B Meyer, Nancy A Benkusky, Martin Kaufmann, Seong Min Lee, Melda Onal, Glenville Jones, J Wesley Pike
The vitamin D endocrine system regulates mineral homeostasis through its activities in the intestine, kidney, and bone. Terminal activation of vitamin D3 to its hormonal form, 1,25(OH)2D3, occurs in the kidney via the cytochrome P450 enzyme CYP27B1. Despite its importance in vitamin D metabolism, the molecular mechanisms underlying the regulation of the gene for this enzyme, Cyp27b1, are unknown. Here, we identified a kidney-specific control module governed by a renal cell-specific chromatin structure located distal to Cyp27b1 that mediates unique basal and parathyroid hormone (PTH)-, fibroblast growth factor 23 (FGF23)-, and 1,25(OH)2D3-mediated regulation of Cyp27b1 expression...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28806419/effects-of-short-term-dry-immersion-on-bone-remodeling-markers-insulin-and-adipokines
#15
Marie-Thérèse Linossier, Liubov E Amirova, Mireille Thomas, Myriam Normand, Marie-Pierre Bareille, Guillemette Gauquelin-Koch, Arnaud Beck, Marie-Claude Costes-Salon, Christine Bonneau, Claude Gharib, Marc-Antoine Custaud, Laurence Vico
BACKGROUND: Dry immersion (DI), a ground-based model of microgravity previously used in Russia, has been recently implemented in France. The aim of this study was to analyze early events in a short-term DI model in which all conditions are met to investigate who is first challenged from osteo- or adipo-kines and to what extent they are associated to insulin-regulating hormones. METHODS: Twelve healthy men were submitted to a 3-day DI. Fasting blood was collected during pre-immersion phase for the determination of the baseline data collection (BDC), daily during DI (DI24h, DI48H and DI72h), then after recovery (R+3h and R+24h)...
2017: PloS One
https://www.readbyqxmd.com/read/28795342/effect-of-cholecalciferol-therapy-on-serum-fgf23-in-vitamin-d-deficient-patients-a-randomized-clinical-trial
#16
T Kamelian, F Saki, M Jeddi, M H Dabbaghmanesh, G H R Omrani
INTRODUCTION: Fibroblast growth factor-23 plays an important role in regulating systemic phosphate homeostasis, and vitamin D metabolism. However, the effect of Cholecalciferol therapy on FGF23 serum level in patients with vitamin D deficiency has not been studied, yet. MATERIALS AND METHODS: This is a double-blind, randomized clinical trial on 119 vitamin D deficient patients in 2016. Biochemical variables of treatment and placebo groups were analyzed after 12 weeks of 50,000 IU of Cholecalciferol vs...
August 9, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28795324/the-fgf23-klotho-axis-and-cardiac-tissue-doppler-imaging-in-pediatric-chronic-kidney-disease-a-prospective-cohort-study
#17
Ylva Tranæus Lindblad, Hannes Olauson, Georgios Vavilis, Ulf Hammar, Maria Herthelius, Jonas Axelsson, Peter Bárány
BACKGROUND: Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is common in pediatric kidney disease patients and a risk factor for future cardiovascular disease (CVD). Fibroblast growth factor-23 (FGF23) and Klotho are novel key players in CKD-MBD, and has been suggested to be involved in the development of CVD. METHODS: This prospective cohort study included 74 pediatric patients; 31 with CKD (age range 0.8-18.8 years, glomerular filtration rate (GFR) range 9-68 mL/min/1...
August 9, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28794403/chronological-immunolocalization-of-sclerostin-and-fgf23-in-the-mouse-metaphyseal-trabecular-and-cortical-bone
#18
Atsunaka Sakurai, Tomoka Hasegawa, Ai Kudo, Zhao Shen, Tomoya Nagai, Miki Abe, Taiji Yoshida, Hiromi Hongo, Tomomaya Yamamoto, Tsuneyuki Yamamoto, Kimimitsu Oda, Paulo Henrique Luiz de Freitas, Minqi Li, Hidehiko Sano, Norio Amizuka
To assess the chronological participation of sclerostin and FGF23 in bone metabolism, this study tracked the immunolocalization of sclerostin and FGF23 in the metaphyses of murine long bones from embryonic day 18 (E18) through 1 day after birth, 1 week, 2 weeks, 4 weeks, 8 weeks, and 20 weeks of age. We have selected two regions in the metaphyseal trabeculae for assessing sclerostin and FGF23 localization: close to the chondro-osseous junction, i.e., bone modeling site even in the adult animals, and the trabecular region distant from the growth plate, where bone remodeling takes place...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28792142/localization-of-oncogenic-osteomalacia-by-systemic-venous-sampling-of-fibroblast-growth-factor-23
#19
Ji Yeon Lee, Hye Sun Park, Seunghee Han, Jiyu Kelly Lim, Namki Hong, Sung Il Park, Yumie Rhee
PURPOSE: Tumor-induced osteomalacia (TIO) is characterized by hypophosphatemia caused by a phosphaturic mesenchymal tumor. While surgical resection of the tumor leads to a cure, identification of the responsible tumor is challenging. Recently, several studies showed that systemic sampling of fibroblast growth factor 23 (FGF23) is helpful for localization of tumors. The present study aimed to evaluate the clinical utility of this method in Korean patients. MATERIALS AND METHODS: Six patients compatible with TIO who were admitted to our hospital between 2006 and 2015 were analyzed...
September 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28782829/the-participation-of-fibroblast-growth-factor-23-fgf23-in-the-progression-of-osteoporosis-via-jak-stat-pathway
#20
Lijun Xu, Lixia Zhang, Huijuan Zhang, Zaigang Yang, Lei Qi, Yurong Wang, Shuxin Ren
Osteoporosis (OP) is a major skeletal disorder for the old man. The fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced by osteoblasts and osteocytes. However, the regulatory mechanisms of FGF23 in the progression of osteoporosis remain poorly understood. This study aims to explore the downstream regulating pathway of FGF23 in postmenopausal osteoporosis. The rat model of osteoporosis was established through ovariectomy (OVX). The investigation demonstrated that the serum levels of FGF23 and the phosphorylation levels of JAK2, STAT1 and STAT3 were up-regulated in the OVX + NVP-BGJ398 group while were down-regulated in the OVX + Anti-FGF23 group than that in the OVX group...
August 7, 2017: Journal of Cellular Biochemistry
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