title: Renal expression of FGF23 in progressive renal disease of diabetes and the effect of ACE inhibitor.
abstract: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone mainly produced by bone that acts in the kidney through FGF receptors and Klotho. Here we investigated whether the kidney was an additional source of FGF23 during renal disease using a model of type 2 diabetic nephropathy. Renal expression of FGF23 and Klotho was assessed in Zucker diabetic fatty (ZDF) and control lean rats at 2, 4, 6, 8 months of age. To evaluate whether the renoprotective effect of angiotensin converting enzyme (ACE) inhibitor in this model was associated with changes in FGF23 and Klotho, ZDF rats received ramipril from 4, when proteinuric, to 8 months of age. FGF23 mRNA was not detectable in the kidney of lean rats, nor of ZDF rats at 2 months of age. FGF23 became measurable in the kidney of diabetic rats at 4 months and significantly increased thereafter. FGF23 protein localized in proximal and distal tubules. Renal Klotho mRNA and protein decreased during time in ZDF rats. As renal disease progressed, serum phosphate levels increased in parallel with decline of fractional phosphorus excretion. Ramipril limited proteinuria and renal injury, attenuated renal FGF23 upregulation and ameliorated Klotho expression. Ramipril normalized serum phosphate levels and tended to increase fractional phosphorus excretion. These data indicate that during progressive renal disease the kidney is a site of FGF23 production which is limited by ACE inhibition. Interfering pharmacologically with the delicate balance of FGF23 and phosphorus in diabetes may have implications in clinics.
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors: Cristina
authors: C
authors: Zanchi
authors: Monica
authors: M
authors: Locatelli
authors: Ariela
authors: A
authors: Benigni
authors: Daniela
authors: D
authors: Corna
authors: Susanna
authors: S
authors: Tomasoni
authors: Daniela
authors: D
authors: Rottoli
authors: Flavio
authors: F
authors: Gaspari
authors: Giuseppe
authors: G
authors: Remuzzi
authors: Carlamaria
authors: C
authors: Zoja
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D019610:Cytoprotection / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005346:Fibroblast Growth Factors / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005966:Glucuronidase / Q000235:genetics; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D000090265:Klotho Proteins; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D050608:Sodium-Phosphate Cotransporter Proteins / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; C505605:Fgf23 protein, rat; D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D005346:Fibroblast Growth Factors; D005966:Glucuronidase; D000090265:Klotho Proteins; D007703:Peptidyl-Dipeptidase A
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