{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T13:46:28Z","timestamp":1781358388180,"version":"3.54.1"},"reference-count":46,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK129431-01A1"],"award-info":[{"award-number":["R01DK129431-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We assessed the involvement of fibroblast growth factor 23 (FGF23) in phosphaturia in sickle cell disease (SCD) mice. Control and SCD mice were treated with FGF23 neutralizing antibody (FGF23Ab) for 24\u2005hours. Serum ferritin was significantly increased in SCD mice and was significantly reduced in female but not male SCD mice by FGF23Ab. FGF23Ab significantly reduced increased erythropoietin in SCD kidneys. Serum intact FGF23 was significantly increased in SCD female mice and was markedly increased in SCD male mice; however, FGF23Ab significantly reduced serum intact FGF23 in both genotypes and sexes. Serum carboxy-terminal-fragment FGF23 (cFGF23) was significantly reduced in SCD IgG male mice and was markedly but not significantly reduced in SCD IgG female mice. FGF23Ab significantly increased cFGF23 in both sexes and genotypes. Serum 1,25-dihydroxyvitamin D3 was significantly increased in SCD IgG and was further significantly increased by FGF23Ab in both sexes and genotypes. Significantly increased blood urea nitrogen in SCD was not reduced by FGF23Ab. The urine phosphate (Pi)\/creatinine ratio was significantly increased in SCD in both sexes and was significantly reduced by FGF23Ab. Increased SCD kidney damage marker kidney injury molecule 1 was rescued, but sclerotic glomeruli, increased macrophages, and lymphocytes were not rescued by short-term FGF23Ab. FGF23Ab significantly reduced increased phospho-fibroblast growth factor receptor 1, \u03b1Klotho, phosphorylated extracellular signal-regulated kinase, phosphorylated serum\/glucocorticoid-regulated kinase 1, phosphorylated sodium-hydrogen exchanger regulatory factor-1, phosphorylated janus kinase 3, and phosphorylated transducer and activator of transcription-3 in SCD kidneys. The type II sodium Pi cotransporter (NPT2a) and sodium-dependent Pi transporter PiT-2 proteins were significantly reduced in SCD kidneys and were increased by FGF23Ab. We conclude that increased FGF23\/FGF receptor 1\/\u03b1Klotho signaling promotes Pi wasting in SCD by downregulating NPT2a and PIT2 via modulation of multiple signaling pathways that could be rescued by FGF23Ab.<\/jats:p>","DOI":"10.1210\/endocr\/bqad173","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T22:40:57Z","timestamp":1700001657000},"source":"Crossref","is-referenced-by-count":4,"title":["Fibroblast Growth Factor 23 Neutralizing Antibody Ameliorates Abnormal Renal Phosphate Handling in Sickle Cell Disease Mice"],"prefix":"10.1210","volume":"164","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9763-3001","authenticated-orcid":false,"given":"Liping","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology and Metabolism, UConn Health School of Medicine , Farmington, CT, 06030 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology and Metabolism, UConn Health School of Medicine , Farmington, CT, 06030 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-4242","authenticated-orcid":false,"given":"Marja M","family":"Hurley","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology and Metabolism, UConn Health School of Medicine , Farmington, CT, 06030 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"issue":"1","key":"2024042101080473200_bqad173-B1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1146\/annurev-pathmechdis-012418-012838","article-title":"Annual review of pathology: mechanisms of disease pathophysiology of sickle cell disease","volume":"14","author":"Sundd","year":"2019","journal-title":"Annu Rev Pathol Mech Dis"},{"issue":"2","key":"2024042101080473200_bqad173-B2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1681\/ASN.2019050502","article-title":"Kidney function decline among black patients with sickle cell trait and sickle cell disease: an observational cohort study","volume":"31","author":"Olaniran","year":"2020","journal-title":"JASN"},{"key":"2024042101080473200_bqad173-B3","doi-asserted-by":"crossref","first-page":"1078853","DOI":"10.3389\/fped.2022.1078853","article-title":"Mineral bone disorders and kidney disease in hospitalized children with sickle cell anemia","volume":"10","author":"Batte","year":"2022","journal-title":"Front Pediatr"},{"issue":"5","key":"2024042101080473200_bqad173-B4","doi-asserted-by":"crossref","first-page":"F1577","DOI":"10.1152\/ajprenal.00463.2006","article-title":"Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro","volume":"293","author":"Perwad","year":"2007","journal-title":"Am J Physiol Renal Physiol"},{"issue":"10","key":"2024042101080473200_bqad173-B5","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/ki.2010.313","article-title":"Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease","volume":"78","author":"Hasegawa","year":"2010","journal-title":"Kidney Int"},{"issue":"12","key":"2024042101080473200_bqad173-B6","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/ki.2011.47","article-title":"Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease","volume":"79","author":"Isakova","year":"2011","journal-title":"Kidney Int"},{"key":"2024042101080473200_bqad173-B7","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3389\/fphys.2019.00304","article-title":"The EPO-FGF23 signaling pathway in erythroid progenitor cells: opening a new area of research","volume":"10","author":"van Vuren","year":"2019","journal-title":"Front Physiol"},{"issue":"6","key":"2024042101080473200_bqad173-B8","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3109\/03630269.2014.967868","article-title":"Erythropoietin levels in patients with sickle cell disease do not correlate with known inducers of erythropoietin","volume":"38","author":"Pulte","year":"2014","journal-title":"Hemoglobin"},{"issue":"11","key":"2024042101080473200_bqad173-B9","doi-asserted-by":"crossref","first-page":"e427","DOI":"10.3324\/haematol.2017.167882","article-title":"Erythropoietin stimulates murine and human fibroblast growth factor-23, revealing novel roles for bone and bone marrow","volume":"102","author":"Clinkenbeard","year":"2017","journal-title":"Haematologica"},{"issue":"5","key":"2024042101080473200_bqad173-B10","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1097\/MNH.0000000000000145","article-title":"FGF23 Regulation of renal tubular solute transport","volume":"24","author":"Erben","year":"2015","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"2024042101080473200_bqad173-B11","doi-asserted-by":"crossref","first-page":"592","DOI":"10.3389\/fendo.2020.00592","article-title":"Osteocytic FGF23 and its kidney function","volume":"11","author":"Agoro","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"3","key":"2024042101080473200_bqad173-B12","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.bone.2012.05.015","article-title":"FGF23 Acts directly on renal proximal tubules to induce phosphaturia through activation of the ERK1\/2-SGK1 signaling pathway","volume":"51","author":"Andrukhova","year":"2012","journal-title":"Bone"},{"key":"2024042101080473200_bqad173-B13","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.molmet.2018.02.007","article-title":"Phosphate-dependent FGF23 secretion is modulated by PIT2\/Slc20a2","volume":"11","author":"Bon","year":"2018","journal-title":"Mol Metab"},{"issue":"5339","key":"2024042101080473200_bqad173-B14","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1126\/science.278.5339.873","article-title":"Knockout-transgenic mouse model of sickle cell disease","volume":"278","author":"Ryan","year":"1997","journal-title":"Science"},{"key":"2024042101080473200_bqad173-B15","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.trsl.2022.10.007","article-title":"Pathophysiological characterization of the Townes mouse model for sickle cell disease","volume":"254","author":"Alvarez-Argote","year":"2023","journal-title":"Transl Res"},{"issue":"4","key":"2024042101080473200_bqad173-B16","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.kint.2018.05.015","article-title":"PiT-2, a type III sodium-dependent phosphate transporter, protects against vascular calcification in mice with chronic kidney disease fed a high phosphate diet","volume":"94","author":"Yamada","year":"2018","journal-title":"Kidney Int"},{"issue":"5","key":"2024042101080473200_bqad173-B17","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1080\/03630269.2016.1224766","article-title":"Renal failure in sickle cell disease: prevalence, predictors of disease, mortality and effect on length of hospital stay","volume":"40","author":"Yeruva","year":"2016","journal-title":"Hemoglobin"},{"issue":"7","key":"2024042101080473200_bqad173-B18","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1002\/jbmr.3417","article-title":"FGF23 Neutralizing antibody partially improves bone mineralization defect of HMWFGF2 isoforms in transgenic female mice","volume":"33","author":"Xiao","year":"2018","journal-title":"J Bone Miner Res"},{"issue":"9","key":"2024042101080473200_bqad173-B19","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1002\/jcb.25493","article-title":"FGFR Inhibitor ameliorates hypophosphatemia and impaired engrailed-1\/Wnt signaling in FGF2 high molecular weight isoform transgenic mice","volume":"117","author":"Du","year":"2016","journal-title":"J Cell Biochem"},{"key":"2024042101080473200_bqad173-B20","article-title":"FGF23 neutralizing antibody ameliorates abnormal renal phosphate handling in sickle cell disease mice-Supplementary Materials and Methods","volume-title":"ZENODO","author":"Xiao"},{"issue":"16","key":"2024042101080473200_bqad173-B21","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1111\/bph.15193","article-title":"The ARRIVE guidelines 2.0: updated guidelines for reporting animal research","volume":"177","author":"du Sert N","year":"2020","journal-title":"Br J Pharmacol"},{"issue":"9","key":"2024042101080473200_bqad173-B22","doi-asserted-by":"crossref","first-page":"991","DOI":"10.5005\/jp-journals-10024-3189","article-title":"Aggravated dental and periodontal Status in patients with sickle cell disease and its association with Serum ferritin","volume":"22","author":"Davidopoulou","year":"2021","journal-title":"J Contemp Dent Pract"},{"issue":"11","key":"2024042101080473200_bqad173-B23","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1210\/jc.2011-1239","article-title":"Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans","volume":"96","author":"Imel","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2024042101080473200_bqad173-B24","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/ki.2015.290","article-title":"Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production","volume":"89","author":"David","year":"2016","journal-title":"Kidney Int"},{"issue":"7","key":"2024042101080473200_bqad173-B25","doi-asserted-by":"crossref","first-page":"3752","DOI":"10.1096\/fj.201700667R","article-title":"Inhibition of fibroblast growth factor 23 (FGF23) signaling rescues renal anemia","volume":"32","author":"Agoro","year":"2018","journal-title":"FASEB J"},{"issue":"7120","key":"2024042101080473200_bqad173-B26","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/nature05315","article-title":"Klotho converts canonical FGF receptor into a specific receptor for FGF23","volume":"444","author":"Urakawa","year":"2006","journal-title":"Nature"},{"issue":"31","key":"2024042101080473200_bqad173-B27","doi-asserted-by":"crossref","first-page":"28265","DOI":"10.1074\/jbc.M202527200","article-title":"Fibroblast growth factor FGF-23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway","volume":"277","author":"Yamashita","year":"2002","journal-title":"J Biol Chem"},{"issue":"4","key":"2024042101080473200_bqad173-B28","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1097\/MNH.0000000000000514","article-title":"Crosstalk between fibroblast growth factor 23, iron, erythropoietin, and inflammation in kidney disease","volume":"28","author":"Babitt","year":"2019","journal-title":"Curr Opin Nephrol Hypertens"},{"issue":"10","key":"2024042101080473200_bqad173-B29","doi-asserted-by":"crossref","first-page":"e0275098","DOI":"10.1371\/journal.pone.0275098","article-title":"Ferritin and its association with anaemia in a healthy adult population in Kenya","volume":"17","author":"Omuse","year":"2022","journal-title":"PLoS One"},{"issue":"8","key":"2024042101080473200_bqad173-B30","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1002\/hep4.2012","article-title":"Iron overload disorders","volume":"6","author":"Hsu","year":"2022","journal-title":"Hepatol Commun"},{"issue":"7","key":"2024042101080473200_bqad173-B31","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.autrev.2007.01.016","article-title":"Ferritin in autoimmune diseases","volume":"6","author":"Zandman-Goddard","year":"2007","journal-title":"Autoimmun Rev"},{"issue":"1","key":"2024042101080473200_bqad173-B32","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.kint.2021.03.019","article-title":"Amelioration of chronic kidney disease-associated anemia by vadadustat in mice is not dependent on erythroferrone","volume":"100","author":"Hanudel","year":"2021","journal-title":"Kidney Int"},{"issue":"12","key":"2024042101080473200_bqad173-B33","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1002\/pbc.25188","article-title":"Abnormalities in renal tubular phosphate handling in children with sickle cell disease","volume":"61","author":"Raj","year":"2014","journal-title":"Pediatr Blood Cancer"},{"issue":"2","key":"2024042101080473200_bqad173-B34","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.3324\/haematol.2016.150987","article-title":"Carboxy-terminal fragment of fibroblast growth factor 23 induces heart hypertrophy in sickle cell disease","volume":"102","author":"Courbebaisse","year":"2017","journal-title":"Haematologica"},{"issue":"21","key":"2024042101080473200_bqad173-B35","doi-asserted-by":"crossref","first-page":"5179","DOI":"10.3390\/jcm10215179","article-title":"Primary hyperparathyroidism in homozygous sickle cell patients: A hemolysis-mediated hypocalciuric hypercalcemia phenotype?","volume":"10","author":"Khan","year":"2021","journal-title":"J Clin Med"},{"issue":"7","key":"2024042101080473200_bqad173-B36","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1681\/ASN.2005010052","article-title":"Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease","volume":"16","author":"Guitierrez","year":"2005","journal-title":"J Am Soc Nephrol"},{"issue":"5","key":"2024042101080473200_bqad173-B37","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1080\/03630269.2016.1224766","article-title":"Renal failure in sickle cell disease: prevalence, predictors of disease, mortality and effect on length of hospital stay","volume":"40","author":"Yeruva","year":"2016","journal-title":"Hemoglobin"},{"issue":"5","key":"2024042101080473200_bqad173-B38","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.3390\/biomedicines11051356","article-title":"Osteopontin as a biomarker in chronic kidney disease","volume":"11","author":"Sinha S","year":"2023","journal-title":"Biomedicines"},{"issue":"10","key":"2024042101080473200_bqad173-B39","doi-asserted-by":"crossref","first-page":"6120","DOI":"10.1074\/jbc.C500457200","article-title":"Regulation of fibroblast growth factor-23 signaling by klotho","volume":"281","author":"Kurosu","year":"2006","journal-title":"J Biol Chem"},{"issue":"1","key":"2024042101080473200_bqad173-B40","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1152\/physrev.00002.2011","article-title":"Regulation and function of the FGF23\/klotho endocrine pathways","volume":"92","author":"Martin","year":"2012","journal-title":"Physiol Rev"},{"issue":"2","key":"2024042101080473200_bqad173-B41","doi-asserted-by":"crossref","first-page":"F282","DOI":"10.1152\/ajprenal.90742.2008","article-title":"FGF23 Decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1","volume":"297","author":"Gattineni","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"issue":"7","key":"2024042101080473200_bqad173-B42","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1210\/jc.2015-1551","article-title":"Prolonged correction of Serum phosphorus in adults with X-linked hypophosphatemia using monthly doses of KRN23","volume":"100","author":"Imel","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2024042101080473200_bqad173-B43","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1677\/JOE-10-0181","article-title":"Altered renal FGF23-mediated activity involving MAPK and Wnt: effects of the Hyp mutation","volume":"207","author":"Farrow","year":"2010","journal-title":"J Endocrinol"},{"issue":"3","key":"2024042101080473200_bqad173-B44","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/jcp.25458","article-title":"FGF23 Neutralizing ameliorates hypophosphatemia and impaired FGF receptor signaling in kidneys of HMWFGF2 transgenic mice","volume":"232","author":"Du","year":"2017","journal-title":"J Cell Physiol"},{"issue":"4","key":"2024042101080473200_bqad173-B45","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/ki.2014.371","article-title":"Janus kinase 3 regulates renal 25-hydroxyvitamin D 1a-hydroxylase expression, calcitriol formation, and phosphate metabolism","volume":"87","author":"Umbach","year":"2015","journal-title":"Kidney Int"},{"issue":"2","key":"2024042101080473200_bqad173-B46","doi-asserted-by":"crossref","first-page":"469","DOI":"10.2337\/db08-1328","article-title":"Enhanced expression of Janus kinase\u2013signal transducer and activator of transcription pathway members in human diabetic nephropathy","volume":"58","author":"Berthier","year":"2009","journal-title":"Diabetes"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/endo\/advance-article-pdf\/doi\/10.1210\/endocr\/bqad173\/53477173\/bqad173.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/164\/12\/bqad173\/57294690\/bqad173.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/164\/12\/bqad173\/57294690\/bqad173.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,21]],"date-time":"2024-04-21T01:08:42Z","timestamp":1713661722000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/doi\/10.1210\/endocr\/bqad173\/7424834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,2]]},"references-count":46,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,11,2]]}},"URL":"https:\/\/doi.org\/10.1210\/endocr\/bqad173","relation":{},"ISSN":["1945-7170"],"issn-type":[{"value":"1945-7170","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,12]]},"published":{"date-parts":[[2023,11,2]]},"article-number":"bqad173"}}