Although fibroblast growth factor 23 (FGF23) acting through its receptor Klotho-FGFR1c decreases parathyroid hormone expression, this hormone is increased in chronic kidney disease despite an elevated serum FGF23. We measured possible factors that might contribute to the resistance of parathyroid glands to FGF23 in rats with the dietary adenine-induced model of chronic kidney disease. Quantitative immunohistochemical and reverse transcription-PCR analysis using laser capture microscopy showed that both Klotho and FGFR1 protein and mRNA levels were decreased in histological sections of the parathyroid glands. Recombinant FGF23 failed to decrease serum parathyroid hormone levels or activate the mitogen-activated protein kinase signaling pathway in the glands of rats with advanced experimental chronic kidney disease. In parathyroid gland organ culture, the addition of FGF23 decreased parathyroid hormone secretion and mRNA levels in control animals or rats with early but not advanced chronic kidney disease. Our results show that because of a downregulation of the Klotho-FGFR1c receptor complex, an increase of circulating FGF23 does not decrease parathyroid hormone levels in established chronic kidney disease. This in vivo resistance is sustained in parathyroid organ culture in vitro. PMID: 20016468 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, SubstancesPublication Types: Research Support, Non-U.S. Gov'tMeSH Terms:Adenine/toxicityAnimalsChronic DiseaseDown-Regulation/geneticsFibroblast Growth Factors/analysisFibroblast Growth Factors/physiology*Glucuronidase/analysisHyperparathyroidism, Secondary/genetics*Kidney Diseases/chemically inducedKidney Diseases/complications*Parathyroid Glands/chemistry*Parathyroid Hormone/analysisRNA, Messenger/analysisRatsReceptor, Fibroblast Growth Factor, Type 1/analysisSubstances:Parathyroid HormoneRNA, Messengerfibroblast growth factor 23Fibroblast Growth FactorsAdenineFgfr1 protein, ratReceptor, Fibroblast Growth Factor, Type 1Glucuronidaseklotho protein LinkOut - more resourcesFull Text Sources:Nature Publishing GroupEBSCOSwets Information ServicesMedical:Kidney Diseases - MedlinePlus Health InformationMolecular Biology Databases:PARATHYROID HORMONE - HSDBSupplemental Content Related citations Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients. [Kidney Int. 2010] Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients. Komaba H, Goto S, Fujii H, Hamada Y, Kobayashi A, Shibuya K, Tominaga Y, Otsuki N, Nibu K, Nakagawa K, et al. Kidney Int. 2010 Feb; 77(3):232-8. Epub 2009 Nov 4.Review FGF23-parathyroid interaction: implications in chronic kidney disease. [Kidney Int. 2010] Review FGF23-parathyroid interaction: implications in chronic kidney disease. Komaba H, Fukagawa M. Kidney Int. 2010 Feb; 77(4):292-8. Epub 2009 Dec 9.FGF23 fails to inhibit uremic parathyroid glands. [J Am Soc Nephrol. 2010] FGF23 fails to inhibit uremic parathyroid glands. Canalejo R, Canalejo A, Martinez-Moreno JM, Rodriguez-Ortiz ME, Estepa JC, Mendoza FJ, Munoz-Castaneda JR, Shalhoub V, Almaden Y, Rodriguez M. J Am Soc Nephrol. 2010 Jul; 21(7):1125-35. Epub 2010 Apr 29.The parathyroid is a target organ for FGF23 in rats. [J Clin Invest. 2007] The parathyroid is a target organ for FGF23 in rats. Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, Goetz R, Kuro-o M, Mohammadi M, Sirkis R, Naveh-Many T, Silver J. J Clin Invest. 2007 Dec; 117(12):4003-8. Review Fibroblast growth factor 23 acts on the parathyroid to decrease parathyroid hormone secretion. [Curr Opin Nephrol Hypertens. 2008] Review Fibroblast growth factor 23 acts on the parathyroid to decrease parathyroid hormone secretion. Galitzer H, Ben-Dov I, Lavi-Moshayoff V, Naveh-Many T, Silver J. Curr Opin Nephrol Hypertens. 2008 Jul; 17(4):363-7. See reviews... See all... All links from this record Related Citations Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.Compound (MeSH Keyword) PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.Gene Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.Gene (GeneRIF) Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.

Department of Nephrology Hadassah Hebrew University Medical Center Jerusalem

Komentář [k článku Další důvod, proč pečlivě kontrolovat sérovou koncentraci fosforu při selhání ledvin: rezistence příštítných tělísek na FGF-23].