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.
Renal Expression of FGF23 in Progressive Renal Disease of Diabetes and the Effect of Ace Inhibitor / C. Zanchi, M. Locatelli, A. Benigni, D. Corna, S. Tomasoni, D. Rottoli, F. Gaspari, G. Remuzzi, C. Zoja. - In: PLOS ONE. - ISSN 1932-6203. - 8:8(2013 Aug), pp. e70775.1-e70775.8.
|Titolo:||Renal Expression of FGF23 in Progressive Renal Disease of Diabetes and the Effect of Ace Inhibitor|
REMUZZI, GIUSEPPE (Penultimo)
|Parole Chiave:||Angiotensin-Converting Enzyme Inhibitors; Animals; Cytoprotection; Diabetes Mellitus, Type 2; Fibroblast Growth Factors; Gene Expression Regulation; Glucuronidase; Kidney; Male; Peptidyl-Dipeptidase A; Phosphates; Rats; Sodium-Phosphate Cotransporter Proteins; Disease Progression; Agricultural and Biological Sciences (all); Biochemistry, Genetics and Molecular Biology (all); Medicine (all)|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
|Data di pubblicazione:||ago-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pone.0070775|
|Appare nelle tipologie:||01 - Articolo su periodico|