title: WT-1 mRNA expression is modulated by nitric oxide availability and Hsp70 interaction after neonatal unilateral ureteral obstruction.
abstract: Wilms tumor gene 1 (wt-1), a key regulator of mesenchymal-epithelial transformation, is downregulated during congenital obstructive nephropathy, leading to apoptosis. There is a functional interaction between WT-1 and inducible nitric oxide synthase (iNOS). In this regard, we reported that after neonatal unilateral ureteral obstruction, rosuvastatin prevents apoptosis through an increase in nitric oxide bioavailability, which in turn is linked to higher Hsp70 expression. Hence, the goal of this study was to determine whether a nitric oxide/Hsp70 interaction is involved in changes in WT-1 mRNA expression after ureteral obstruction. Neonatal rats submitted to experimental ureteral obstruction were treated with either vehicle or rosuvastatin for 14 days. Decreased nitric oxide and iNOS/Hsp70 expression associated with WT-1 low expression was shown in obstructed kidneys. Apoptosis was induced and it was associated with an increased Bax/BcL2 ratio. Conversely, iNOS/Hsp70 upregulation and an increased WT-1 mRNA expression, without an apoptotic response, were observed in the cortex of obstructed kidneys of rosuvastatin-treated rats. Nitric oxide also modulated Hsp70 and WT-1 mRNA expression in MDCK cells. Finally, in vivo experiments with nitric oxide modulators support our hypothesis that WT-1 mRNA expression is associated with nitric oxide level. Results suggest that rosuvastatin may modulate WT-1 mRNA expression through renal nitric oxide bioavailability, preventing neonatal obstruction-induced apoptosis associated with Hsp70 interaction.
authors: Area de Fisiopatología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina.
authors: Luciana
authors: L
authors: Mazzei
authors: Isabel Mercedes
authors: IM
authors: García
authors: Valeria
authors: V
authors: Cacciamani
authors: María Eugenia
authors: ME
authors: Benardón
authors: Walter
authors: W
authors: Manucha
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004195:Disease Models, Animal; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D008165:Luminol / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014517:Ureteral Obstruction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005464:Fluorobenzenes; D018840:HSP70 Heat-Shock Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009842:Oligopeptides; D011743:Pyrimidines; D013449:Sulfonamides; D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins; D009569:Nitric Oxide; D008165:Luminol; D000068718:Rosuvastatin Calcium; C036212:S 2613; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester