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https://www.readbyqxmd.com/read/27890549/novel-functions-of-circulating-klotho
#1
REVIEW
Julia M Hum, Linda O'Bryan, Rosamund C Smith, Kenneth E White
A significant portion of the key biological functions of αKlotho (αKL) and its cognate ligand Fibroblast growth factor-23 (FGF23) have been revealed through the study of rare diseases of mineral metabolism. These findings have far reaching implications for common disorders such as chronic kidney disease-mineral bone disorder (CKD-MBD). αKL's predominant effect on mineral homeostasis is through its actions in the kidney as a co-receptor for FGF23, however emerging data has shed light on its capacity to act as a circulating factor through the cleavage of the transmembrane form of αKL ('mKL') to produce 'cleaved KL' or 'cKL'...
November 23, 2016: Bone
https://www.readbyqxmd.com/read/27878865/fibroblast-growth-factor-21-night-watch-advances-and-uncertainties-in-the-field
#2
REVIEW
A Kharitonenkov, R DiMarchi
Fibroblast growth factor (FGF) 21 belongs to a hormone-like subgroup within the FGF superfamily. The members of this subfamily, FGF19, FGF21 and FGF23, are characterized by their reduced binding affinity for heparin that enables them to be transported in the circulation and function in an endocrine manner. It is likely that FGF21 also acts in an autocrine and paracrine fashion, as multiple organs can produce this protein and its plasma concentration seems to be below the level necessary to induce a pharmacological effect...
November 22, 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27871077/impact-of-annexin-a-7-deficiency-on-fgf23-plasma-concentrations
#3
Anja T Umbach, Omar El-Attar, Dong Luo, Hajar Fakhri, Rosi Bissinger, Florian Lang
BACKGROUND/AIMS: The release of fibroblast growth factor FGF23, a powerful regulator of 1,25(OH)2D3 formation and mineral metabolism, is stimulated by store-operated Ca2+ entry (SOCE), which is accomplished by the pore forming Ca2+ release activated channel protein Orai1. Regulators of Orai1 and thus FGF23 release include serum & glucocorticoid inducible kinase SGK1, a kinase up-regulated by glucocorticosteroids. Some effects of glucocorticoids require the presence of annexin A7, such as suppression of prostaglandin E2 in gastric glands...
November 21, 2016: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/27867811/dramatic-mitigation-of-bone-pain-after-phosphorus-replacement-therapy-in-a-subject-with-fgf23-related-hypophosphatemic-osteomalacia
#4
Fuminori Tatsumi, Megumi Horiya, Akihito Tanabe, Momoyo Nishioka, Yoshiro Fushimi, Junpei Sanada, Yurie Hirata, Shintaro Irie, Tomoe Kinoshita, Shinji Kamei, Masashi Shimoda, Tomoatsu Mune, Kohei Kaku, Hideaki Kaneto
INTRODUCTION: Fibroblast growth factor 23 (FGF23) is secreted from bone and suppresses the absorption of phosphorus in renal proximal tubule and in intestinal tract. Therefore, the increase of serum FGF23 levels leads to hypophosphatemic situations. Tumor-induced osteomalacia is often induced by various tumors, but it is often difficult to identify the localization of tumor, because most of the FGF23-producing tumors are small and could be observed in any part of the body. CASE DESCRIPTION: Here we report a case of elderly female subject with FGF23-related hypophosphatemic osteomalacia who repeatedly experienced severe bone pain and fragility fracture in various parts of the body...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27867679/identification-of-two-novel-mutations-in-the-galnt3-gene-in-a-chinese-family-with-hyperphosphatemic-familial-tumoral-calcinosis
#5
Lihao Sun, Lin Zhao, Lianjun Du, Peipei Zhang, Minjia Zhang, Min Li, Tingting Liu, Lei Ye, Bei Tao, Hongyan Zhao, Jianmin Liu, Xiaoyi Ding
Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare, autosomal recessive genetic disease. This disease is characterized by the progressive calcification of soft tissues leading to symptoms of pressure and hyperphosphatemia but normal concentrations of serum calcium with or without an elevation of 1,25-dihydroxyvitamin D3 levels.HFTC is caused by loss-of-function mutations in the GALNT3, FGF23 or KL genes. Here, we identified two novel mutations in the GALNT3 gene in a Chinese family with HFTC. Identification of a novel genotype in HFTC provides clues for understanding the phenotype-genotype relationships in HFTC and may assist not only in the clinical diagnosis of HFTC but also in the interpretation of the genetic information used for prenatal diagnosis and genetic counseling...
2016: Bone Research
https://www.readbyqxmd.com/read/27862258/raine-syndrome-omim-259775-caused-by-fam20c-mutation-is-congenital-sclerosing-osteomalacia-with-cerebral-calcification-omim-259660
#6
Michael P Whyte, William H McAlister, Michael D Fallon, Mary Ella Pierpont, Vinieth N Bijanki, Shenghui Duan, Ghada A Otaify, William S Sly, Steven Mumm
In 1985, we briefly reported infant sisters with a unique, lethal, autosomal recessive disorder designated congenital sclerosing osteomalacia with cerebral calcification. In 1986, this condition was entered into Mendelian Inheritance In Man (MIM) as osteomalacia, sclerosing, with cerebral calcification (MIM 259660). However, no attestations followed. Instead, in 1989 Raine and colleagues published an affected neonate considering unprecedented the striking clinical and radiographic features. In 1992, "Raine syndrome" entered MIM formally as osteosclerotic bone dysplasia, lethal (MIM #259775)...
November 10, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27861335/response-of-fibroblast-growth-factor-23-to-volume-interventions-in-arterial-hypertension-and-diabetic-nephropathy
#7
Jelmer K Humalda, Sarah Seiler-Muler, Arjan J Kwakernaak, Marc G Vervloet, Gerjan Navis, Danilo Fliser, Gunnar H Heine, Martin H de Borst
Fibroblast growth factor 23 (FGF-23) rises progressively in chronic kidney disease and is associated with adverse cardiovascular outcomes. FGF-23 putatively induces volume retention by upregulating the sodium-chloride cotransporter (NCC). We studied whether, conversely, interventions in volume status affect FGF-23 concentrations.We performed a post hoc analysis of 1) a prospective saline infusion study with 12 patients with arterial hypertension who received 2 L of isotonic saline over 4 hours, and 2) a randomized controlled trial with 45 diabetic nephropathy (DN) patients on background angiotensin-converting enzyme -inhibition (ACEi), who underwent 4 6-week treatment periods with add-on hydrochlorothiazide (HCT) or placebo, combined with regular sodium (RS) or low sodium (LS) diet in a cross-over design...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27852236/effects-of-intravenous-iron-on-fibroblast-growth-factor-23-fgf23-in-haemodialysis-patients-a-randomized-controlled-trial
#8
Matthew A Roberts, Louis Huang, Darren Lee, Robert MacGinley, Stefanie M A Troster, Annette B Kent, Sukhvinder S Bansal, Iain C Macdougall, Lawrence P McMahon
BACKGROUND: Intravenous iron affects serum levels of intact fibroblast growth factor-23 (iFGF23) and its cleavage product c-terminal FGF23 (cFGF23) in iron-deficient people with normal renal function. We hypothesized that intravenous iron modulates iFGF23 and cFGF23 in haemodialysis patients differently according to the type of iron used. METHODS: Prevalent, stable haemodialysis patients requiring protocol-based intravenous iron therapy were randomized to a single 200 mg dose of either ferric carboxymaltose (FCM) or iron sucrose (IS)...
November 16, 2016: BMC Nephrology
https://www.readbyqxmd.com/read/27848940/parenteral-iron-polymaltose-changes-i-c-terminal-fgf23-ratios-in-iron-deficiency-but-not-in-dialysis-patients
#9
S-J Tan, S Satake, E R Smith, N D Toussaint, T D Hewitson, S G Holt
BACKGROUND/OBJECTIVES: Iron and phosphate are both vital to many biological cellular processes with central roles in energy metabolism, cellular proliferation and nucleic acid synthesis. Regulatory pathways in some of these metabolic pathways may intersect at fibroblast growth factor 23 (FGF23), a major phosphate regulatory hormone. Iron is reported to induce hypophosphataemia in rare cases, and recent reports suggest that iron deficiency may upregulate FGF23 synthesis by mechanisms involving hypoxia-inducible factor 1α (HIF1α)...
November 16, 2016: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/27847255/fgf23-%C3%AE-klotho-as-a-paradigm-for-a-kidney-bone-network
#10
REVIEW
Makoto Kuro-O, Orson W Moe
The vertebrate endoskeleton is not a mere frame for muscle attachment to facilitate locomotion, but is a massive organ integrated with many physiologic functions including mineral and energy metabolism. Mineral balance is maintained by tightly controlled ion fluxes that are external (intestine and kidney) and internal (between bone and other organs), and are regulated and coordinated by many endocrine signals between these organs. The endocrine fibroblast growth factors (FGFs) and Klotho gene families are complex systems that co-evolved with the endoskeleton...
November 12, 2016: Bone
https://www.readbyqxmd.com/read/27847254/vascular-calcification-in-ckd-mbd-roles-for-phosphate-fgf23-and-klotho
#11
REVIEW
Shunsuke Yamada, Cecilia M Giachelli
Vascular calcification (VC) is highly prevalent in aging, diabetes mellitus, and chronic kidney disease (CKD). VC is a strong predictor of cardiovascular morbidity and mortality in the CKD population. Complex pathological mechanisms are involved in the development of VC, including osteochondrogenic differentiation and apoptosis of vascular smooth muscle cells, instability and release of extracellular vesicles loaded calcium and phosphate, and elastin degradation. Elevated serum phosphate is a late manifestation of CKD, and has been shown to accelerate mineral deposition in both the vessel wall and heart valves...
November 12, 2016: Bone
https://www.readbyqxmd.com/read/27837149/chronic-hyperphosphatemia-and-vascular-calcification-are-reduced-by-stable-delivery-of-soluble-klotho
#12
Julia M Hum, Linda M O'Bryan, Arun K Tatiparthi, Taryn A Cass, Erica L Clinkenbeard, Martin S Cramer, Manoj Bhaskaran, Robert L Johnson, Jonathan M Wilson, Rosamund C Smith, Kenneth E White
αKlotho (αKL) regulates mineral metabolism, and diseases associated with αKL deficiency are characterized by hyperphosphatemia and vascular calcification (VC). αKL is expressed as a membrane-bound protein (mKL) and recognized as the coreceptor for fibroblast growth factor-23 (FGF23) and a circulating soluble form (cKL) created by endoproteolytic cleavage of mKL. The functions of cKL with regard to phosphate metabolism are unclear. We tested the ability of cKL to regulate pathways and phenotypes associated with hyperphosphatemia in a mouse model of CKD-mineral bone disorder and αKL-null mice...
November 11, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27836924/spleen-contributes-significantly-to-increased-circulating-levels-of-fibroblast-growth-factor23-in-response-to-lipopolysaccharide-induced-inflammation
#13
Shweta Bansal, William E Friedrichs, Chakradhar Velagapudi, Denis Feliers, Khaled Khazim, Diane Horn, John E Cornell, Sherry L Werner, Paolo Fanti
BACKGROUND: Circulating levels of fibroblast growth factor 23 (FGF23) increase progressively and correlate with systemic inflammation in chronic kidney disease (CKD). The aim of this study was to identify and characterize the causal relationship between FGF23 and inflammation in CKD. METHODS: Circulating FGF23 and inflammatory cytokines were correlated in healthy subjects and patients with varying levels of CKD. In addition, FGF23 expression in blood and solid organs was measured in normal mice that were exposed acutely (one time) or chronically (2-week) to low-dose lipopolysaccharide (LPS); chronic exposure being either sustained (subcutaneous pellets), intermittent (daily injections) or combined sustained plus acute (subcutaneous pellets plus acute injection on the day of sacrifice)...
November 10, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/27832316/bone-derived-factors-a-new-gateway-to-regulate-glycemia
#14
Nicolas Bonnet
Type 2 diabetes mellitus (T2DM) and osteoporosis are two major disorders which prevalence increases with aging and is predicted to worsen in the coming years. Preclinical investigations suggest common mechanisms implicated in the pathogenesis of both disorders. Recent evidence has established that there is a clear link between glucose and bone metabolism. The emergence of bone as an endocrine regulator through FGF23 and osteocalcin has led to the re-evaluation of the role of bone cells and bone-derived factors in the development of metabolic diseases such as T2DM...
November 10, 2016: Calcified Tissue International
https://www.readbyqxmd.com/read/27826644/novel-faces-of-fibroblast-growth-factor-23-fgf23-iron-deficiency-inflammation-insulin-resistance-left-ventricular-hypertrophy-proteinuria-and-acute-kidney-injury
#15
Mehmet Kanbay, Marc Vervloet, Mario Cozzolino, Dimitrie Siriopol, Adrian Covic, David Goldsmith, Yalcin Solak
FGF23 is a hormone that appears as the core regulator of phosphate metabolism. Great deal of data has accumulated to demonstrate increased FGF23 secretion from the bone to compensate for even subtle increases in serum phosphorus long before intact PTH. However, recent evidence points to the fact that actions and interactions of FGF23 are not limited solely to phosphate metabolism. FGF23 may be implicated in iron metabolism and erythropoiesis, inflammation, insulin resistance, proteinuria, acute kidney injury and left ventricular hypertrophy...
November 9, 2016: Calcified Tissue International
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
#16
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/27812184/vitamin-d-fibroblast-growth-factor-23-and-incident-cognitive-impairment-findings-from-the-regards-study
#17
Bhupesh Panwar, Suzanne E Judd, Virginia J Howard, Nancy S Jenny, Virginia G Wadley, Orlando M Gutiérrez
Vitamin D protects against cognitive decline in animals but evidence in humans has been inconsistent. Fibroblast growth factor 23 (FGF23) is a hormone that inhibits vitamin D activation yet few studies examined whether FGF23 is associated with cognitive impairment. The objective of this study was to examine associations of 25(OH)D and FGF23 with incident cognitive impairment in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white adults ≥45 years old. FGF23 and 25(OH)D were measured in 474 incident impairment cases and 561 controls...
2016: PloS One
https://www.readbyqxmd.com/read/27807212/the-pas-de-trois-of-vitamin-d-fgf23-and-pth
#18
EDITORIAL
Tally Naveh-Many, Justin Silver
No abstract text is available yet for this article.
November 2, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27803896/roles-of-fgf-signals-in-heart-development-health-and-disease
#19
REVIEW
Nobuyuki Itoh, Hiroya Ohta, Yoshiaki Nakayama, Morichika Konishi
The heart provides the body with oxygen and nutrients and assists in the removal of metabolic waste through the blood vessels of the circulatory system. It is the first organ to form during embryonic morphogenesis. FGFs with diverse functions in development, health, and disease are signaling proteins, mostly as paracrine growth factors or endocrine hormones. The human/mouse FGF family comprises 22 members. Findings obtained from mouse models and human diseases with FGF signaling disorders have indicated that several FGFs are involved in heart development, health, and disease...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27784318/dietary-phosphate-supplement-does-not-rescue-skeletal-phenotype-in-a-mouse-model-for-craniometaphyseal-dysplasia
#20
Yaling Liu, Eliane H Dutra, Ernst J Reichenberger, I-Ping Chen
BACKGROUND: Mutations in the human progressive ankylosis gene (ANKH; Mus musculus ortholog Ank) have been identified as cause for craniometaphyseal dysplasia (CMD), characterized by progressive thickening of craniofacial bones and flared metaphyses of long bones. We previously reported a knock-in (KI) mouse model (Ank (KI/KI)) for CMD and showed transiently lower serum phosphate (Pi) as well as significantly higher mRNA levels of fibroblast growth factor 23 (Fgf23) in Ank (KI/KI) mice...
October 26, 2016: Journal of Negative Results in Biomedicine
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