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F Saki, S R Kasaee, F Sadeghian, F Koohpeyma, G H R Omrani
BACKGROUND: Testosterone deficiency might be associated with vitamin D levels in hypogonadal men, but it is not clear whether testosterone can affect vitamin D and fibroblast growth factor-23 (FGF23), either directly or indirectly via aromatization to estradiol. We aimed to investigate the role of testosterone on vitamin D metabolism and serum FGF23 in male rats. METHODS: A total of 48 male rats were divided into 4 equal groups: sham; O, orchiectomy; O + T, orchiectomized rats treated with testosterone; and O + T + L, orchiectomized rats treated with combination of testosterone and letrozole...
March 20, 2018: Journal of Endocrinological Investigation
Keith G Avin, Julian A Vallejo, Neal X Chen, Kun Wang, Chad D Touchberry, Marco Brotto, Sarah L Dallas, Sharon M Moe, Michael J Wacker
Skeletal muscle dysfunction accompanies the clinical disorders of chronic kidney disease (CKD) and hereditary hypophosphatemic rickets. In both disorders fibroblast growth factor 23 (FGF23), a bone-derived hormone regulating phosphate and vitamin D metabolism, becomes chronically elevated. FGF23 has been shown to play a direct role in cardiac muscle dysfunction; however, it is unknown whether FGF23 signaling can also directly induce skeletal muscle dysfunction. We found expression of potential FGF23 receptors ( Fgfr1-4) and α-Klotho in muscles of two animal models (CD-1 and Cy/+ rat, a naturally occurring rat model of Chronic Kidney Disease-Mineral Bone Disorder) as well as C2 C12 myoblasts and myotubes...
March 20, 2018: American Journal of Physiology. Endocrinology and Metabolism
Nina Bon, Giulia Frangi, Sophie Sourice, Jérôme Guicheux, Sarah Beck-Cormier, Laurent Beck
OBJECTIVE: The canonical role of the bone-derived fibroblast growth factor 23 (Fgf23) is to regulate the serum inorganic phosphate (Pi) level. As part of a feedback loop, serum Pi levels control Fgf23 secretion through undefined mechanisms. We recently showed in vitro that the two high-affinity Na+ -Pi co-transporters PiT1/Slc20a1 and PiT2/Slc20a2 were required for mediating Pi-dependent signaling. Here, we addressed the contribution of PiT1 and PiT2 to the regulation of Fgf23 secretion...
February 26, 2018: Molecular Metabolism
Jarrod M Zamparini, Andrew R Immelman, Frederick J Raal
BACKGROUND: Patients with homozygous familial hypercholesterolemia (HoFH) develop significant vascular calcification early in life, the cause of which is not yet fully understood. Patients with chronic kidney disease have similar vascular calcification, with fibroblast growth factor-23 (FGF23) implicated in these patients. OBJECTIVE: To determine whether there was a difference in FGF23 between patients with HoFH and age- and gender-matched controls and whether there is a correlation between FGF23 and serum low-density lipoprotein, total cholesterol, and carotid intima-media thickness in patients with HoFH...
February 16, 2018: Journal of Clinical Lipidology
Patrícia T Goldenstein, Precil D Neves, Bruno E Balbo, Rosilene M Elias, Alexandre C Pereira, Luiz F Onuchic, Harald Jüppner, Vanda Jorgetti, Hugo Abensur, Rosa Maria Moysés
Primary tumoral calcinosis is a rare autosomal recessive disorder characterized by ectopic calcified tumoral masses. Mutations in 3 genes (GALNT3, FGF23, and KL) have been linked to this human disorder. We describe a case of a 28-year-old man with a history of painful firm masses over his right and left gluteal region, right clavicle region, knees, and left elbow. Biochemical analysis disclosed hyperphosphatemia (phosphate, 9.0 mg/dL) and normocalcemia (calcium, 4.8 mg/dL), with normal kidney function and fractional excretion of phosphate of 3%...
March 14, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Marie Paquet, Mathieu Gauthé, Jules Zhang Yin, Valérie Nataf, Ophélie Bélissant, Philippe Orcel, Christian Roux, Jean-Noël Talbot, Françoise Montravers
PURPOSE: Oncogenic osteomalacia is an endocrine disorder induced by small benign tumours (TIO) producing excessive fibroblast growth factor-23 (FGF23). The only way of curing oncogenic osteomalacia is surgical resection of the culprit TIO, which is extremely difficult to detect using conventional imaging modalities due to its small size and variable location in the body. Since TIO frequently overexpress somatostatin receptors, a clinical utility of SPECT or PET with radiolabelled somatostatin analogues has been reported...
March 12, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Amany M El-Saeed, Ghada F El-Mohasseb
Diabetic nephropathy (DN) is a progressive kidney disease. Previous studies reported that microalbuminuria might not be a sufficient marker to identify diabetic patients at risk of kidney disease progression. Fibroblast growth factors 21 (FGF21) and 23 (FGF23) may play an important role in the DN development and progression. We aimed to assess levels of FGF21 and FGF23 in patients with type 2 diabetes (T2D) with normoalbuminurea, to determine their association with other biochemical parameters and to verify their role as contributing factors to development of DN...
June 2017: Egyptian Journal of Immunology
Bahar Gürlek Demirci, Siren Sezer, Saliha Uyanık Yıldırım, Meltem Kaynar Erdoğan, Emre Tutal, Özlem Özdemir, Gani Orazbayev, Mehmet Haberal
OBJECTIVES: Increased circulating levels of fibroblast growth factor 23, neutrophil gelatinase-associated lipocalin, and endostatin are independent risk factors for cardiovascular disease. Here, we evaluated correlations among these parameters and graft dysfunction and their relation with arterial stiffness. MATERIALS AND METHODS: This prospective study included 73 maintenance kidney transplant patients with stable allograft function who had received the transplant at least 36 months previously...
March 2018: Experimental and Clinical Transplantation
Melda Onal, Alex H Carlson, Jeff D Thostenson, Nancy A Benkusky, Mark B Meyer, Seong M Lee, J Wesley Pike
Fibroblast growth factor 23 (FGF23) production is regulated by both calciotropic hormones and inflammation. Consistent with this, elevated FGF23 levels are associated with inflammatory markers as well as parathyroid hormone (PTH) in various disease states, including chronic kidney disease (CKD). However, the molecular mechanisms underpinning Fgf23 transcription in response to these regulators are largely unknown. We therefore utilized chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) data from an osteocyte cell line to identify potential regulatory regions of the Fgf23 gene...
January 2018: JBMR Plus
David E Leaf, Edward D Siew, Michele F Eisenga, Karandeep Singh, Finnian R Mc Causland, Anand Srivastava, T Alp Ikizler, Lorraine B Ware, Adit A Ginde, John A Kellum, Paul M Palevsky, Myles Wolf, Sushrut S Waikar
BACKGROUND AND OBJECTIVES: Dysregulated mineral metabolism is a common and potentially maladaptive feature of critical illness, especially in patients with AKI, but its association with death has not been comprehensively investigated. We sought to determine whether elevated plasma levels of the osteocyte-derived, vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23), are prospectively associated with death in critically ill patients with AKI requiring RRT, and in a general cohort of critically ill patients with and without AKI...
March 8, 2018: Clinical Journal of the American Society of Nephrology: CJASN
Hidekazu Sugiura, Ai Matsushita, Mayuko Futaya, Atsuko Teraoka, Ken-Ichi Akiyama, Noriyoshi Usui, Nobuo Nagano, Kosaku Nitta, Ken Tsuchiya
The hormone fibroblast growth factor 23 (FGF23) is secreted from bone and is involved in phosphorus (P) metabolism. FGF23 mainly binds the FGF receptor, which interacts with αKlotho in the kidney or parathyroid and regulates Na-dependent phosphate co-transporter type IIa (NaPi-IIa) and type IIc (NaPi-IIc) expression, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) activity, and parathyroid hormone (PTH) secretion. In this study, we utilized hemi-nephrectomized rats fed a high-P diet (HP Nx), rats subjected to a partial nephrectomy (PN) and rats with doxorubicin-induced renal failure (DXR) as chronic kidney disease (CKD) animal models and analyzed the P metabolism and FGF23 expression in the kidneys in each CKD model...
2018: PloS One
Bhupesh Panwar, Suzanne E Judd, Virginia G Wadley, Nancy S Jenny, Virginia J Howard, Monika M Safford, Orlando M Gutiérrez
Importance: Higher circulating fibroblast growth factor 23 (FGF23) concentrations are associated with cardiovascular disease events linked to heart failure, but associations of FGF23 with coronary heart disease (CHD) have been less consistent. Objective: To determine the association of plasma FGF23 concentrations with incident CHD and whether this association differs by race, sex, or chronic kidney disease status. Design, Setting, and Participants: We examined the association of FGF23 concentrations with incident CHD risk within the Reasons for Geographic and Racial Differences in Stroke study, a prospective cohort of black and white adults 45 years and older enrolled between January 2003 and October 2007 with follow-up through December 31, 2011...
March 7, 2018: JAMA Cardiology
Seiji Fukumoto
Fibroblast growth factor 23 (FGF23) is a phosphotropic hormone mainly produced by bone. FGF23 reduces serum phosphate by suppressing intestinal phosphate absorption through reducing 1,25-dihydroxyvitamin D and proximal tubular phosphate reabsorption. Excessive actions of FG23 result in several kinds of hypophosphatemic rickets/osteomalacia including X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia. While neutral phosphate and active vitamin D are standard therapies for child patients with XLH, these medications have several limitations both in their effects and adverse events...
2018: Frontiers in Endocrinology
Kimberley N Sent-Doux, Craig Mackinnon, Jen-Chieh Lee, Andrew L Folpe, Omar Habeeb
Phosphaturic Mesenchymal Tumor (PMT) is a rare, histologically distinctive neoplasm, which classically presents with phosphaturia and tumor-induced osteomalacia (TIO) (i.e., oncogenic osteomalacia). Both the phosphaturia and TIO are due to paraneoplastic production of FGF23 (a phosphatonin) by the neoplastic cells, which are genetically characterized by rearrangements of FN1 (most often with FGFR1 - and less frequently with FGF1). However, rare cases of PMT present without phosphaturia and TIO (i.e., the "non-phosphaturic" variant) - and are therefore much more challenging to diagnose...
March 4, 2018: Human Pathology
Seiji Fukumoto
Osteocytes have several functions such as sensing mechanical load to bone and regulating osteoclastic bone resorption. In addition, osteocytes secrete several humoral factors that affect bone and other organs. FGF23 produced by osteocytes works as a hormone that reduces serum phosphate level. Sclerostin suppresses bone formation by inhibiting Wnt signals. Drugs that inhibit the activities of these factors are now under investigation as new therapeutic measures.
2018: Clinical Calcium
Sezer Acar, Huda A BinEssa, Korcan Demir, Roua A Al-Rijjal, Minjing Zou, Gönül Çatli, Ahmet Anık, Anwar F Al-Enezi, Seçil Özışık, Manar S A Al-Faham, Ayhan Abacı, Bumin Dündar, Walaa E Kattan, Maysoon Alsagob, Salih Kavukçu, Hamdi E Tamimi, Brian F Meyer, Ece Böber, Yufei Shi
BACKGROUND: Hereditary hypophosphatemia is a group of rare renal phosphate wasting disorders. The diagnosis is based on clinical, radiological, and biochemical features, and may require genetic testing to be confirmed. METHODOLOGY: Clinical features and mutation spectrum were investigated in patients with hereditary hypophosphatemia. Genomic DNA of 23 patients from 15 unrelated families were screened sequentially by PCR-sequencing analysis for mutations in the following genes: PHEX, FGF23, DMP1, ENPP1, CLCN5, SLC34A3 and SLC34A1...
2018: PloS One
Liping Xiao, Collin Homer-Bouthiette, Marja M Hurley
Mice overexpressing high molecular weight FGF2 isoforms (HMWTg) in osteoblast lineage phenocopy human X-linked hypophosphatemic rickets (XLH) and Hyp murine model of XLH demonstrating increased FGF23/FGF receptor signaling and hypophosphatemic rickets/osteomalacia. Since HMWFGF2 was up-regulated in bones of Hyp mice and abnormal FGF23 signaling is important in XLH, HMWTg mice were used to examine the effect of the FGF23 neutralizing antibody (FGF23Ab). Eight-week-old female Vector control mice and HMWTg mice were treated with FGF23Ab or control IgG...
March 4, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Ganesh Pathare, Manuel Anderegg, Giuseppe Albano, Florian Lang, Daniel G Fuster
Fibroblast growth factor 23 (FGF23) participates in the orchestration of mineral metabolism by inducing phosphaturia and decreasing the production of 1,25(OH)2 D3 . It is known that FGF23 release is stimulated by aldosterone and extracellular volume depletion. To characterize this effect further in a model of mild hypovolemia, we studied mice lacking the thiazide sensitive NaCl cotransporter (NCC). Our data indicate that NCC knockout mice (KO) have significantly higher FGF23, PTH and aldosterone concentrations than corresponding wild type (WT) mice...
February 26, 2018: Scientific Reports
Christian Lerch, Rukshana Shroff, Mandy Wan, Lesley Rees, Helen Aitkenhead, Ipek Kaplan Bulut, Daniela Thurn, Aysun Karabay Bayazit, Anna Niemirska, Nur Canpolat, Ali Duzova, Karolis Azukaitis, Ebru Yilmaz, Fatos Yalcinkaya, Jerome Harambat, Aysel Kiyak, Harika Alpay, Sandra Habbig, Ariane Zaloszyc, Oguz Soylemezoglu, Cengiz Candan, Alejandra Rosales, Anette Melk, Uwe Querfeld, Maren Leifheit-Nestler, Anja Sander, Franz Schaefer, Dieter Haffner
Background: We investigated the effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism, i.e. serum levels of fibroblast growth factor 23 (FGF23), Klotho, bone alkaline phosphatase (BAP) and sclerostin, in two cohorts with chronic kidney disease (CKD). Methods: In all, 80 vitamin D-deficient children were selected: 40 with mild to moderate CKD from the ERGO study, a randomized trial of ergocalciferol supplementation [estimated glomerular filtration rate (eGFR) 55 mL/min/1...
February 21, 2018: Nephrology, Dialysis, Transplantation
Rafiou Agoro, Anna Montagna, Regina Goetz, Onyedikachi Aligbe, Gurinder Singh, Lindsay M Coe, Moosa Mohammadi, Stefano Rivella, Despina Sitara
Severe anemia and iron deficiency are common complications in chronic kidney disease. The cause of renal anemia is multifactorial and includes decreased erythropoietin (Epo) production, iron deficiency, and inflammation, and it is currently treated with injections of synthetic Epo. However, the use of recombinant Epo has several adverse effects. We previously reported that high fibroblast growth factor 23 (FGF23) levels in mice are associated with decreased red blood cell production, whereas genetic inactivation of Fgf23 results in expansion of the erythroid lineage...
February 26, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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