title: Advanced glycation end products stimulate gene expression of fibroblast growth factor 23.
abstract: Osteoblasts produce fibroblast growth factor 23 (FGF23), a hormone inhibiting renal phosphate reabsorption and the formation of biologically active vitamin D, calcitriol. FGF23-deficient mice age rapidly and develop age-associated diseases at least in part due to massive calcification. Elevated FGF23 serum levels are detected in patients suffering from acute and chronic renal, cardiovascular, inflammatory, and metabolic diseases. Advanced glycation end products (AGEs) are sugar-modified proteins, nucleic acid, and lipids which contribute to these disorders. Here, we studied the significance of AGEs for the generation of FGF23.
  
  
  
  As AGE sources, bread crust extract (BCE) and ribose-modified bovine serum albumin (r-BSA) were used. UMR106 osteoblast-like cells were exposed to BCE and r-BSA, and Fgf23 transcripts were determined by qRT-PCR. UMR106 cells express the receptor for AGEs, RAGE. BCE and r-BSA were powerful stimulators of Fgf23 transcription. NFκB inhibitor wogonin and store-operated calcium entry (SOCE) antagonist 2-APB attenuated the r-BSA and BCE effects on FGF23 synthesis.
  
  
  
  Sources of AGEs induce the transcription of Fgf23 in UMR cells. At least in part, the effect is mediated through up-regulation of NFκB and subsequent SOCE. AGE-induced FGF23 production may contribute to increased FGF23 serum levels observed in chronic disease.
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Ludmilla
authors.initials: L
authors.lastname: Bär
authors.affiliation: Department of Heart Surgery, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Wächter
authors.affiliation: Department of Heart Surgery, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Wege
authors.affiliation: Center for Basic Medical Research, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Navarrete Santos
authors.affiliation: Department of Heart Surgery, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Simm
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
mesh_terms: D000818:Animals; D001939:Bread; D045744:Cell Line, Tumor; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics; D012266:Ribose / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: C000593874:Ager protein, rat; C000717428:Fgf23 protein, mouse; C505605:Fgf23 protein, rat; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D012710:Serum Albumin, Bovine; D005346:Fibroblast Growth Factors; D012266:Ribose; D000089703:Fibroblast Growth Factor-23
keywords: Calcium; Diabetes; Inflammation; Phosphate; Vitamin D