WT-1 mRNA expression is modulated by nitric oxide availability and Hsp70 interaction after neonatal unilateral...

Area of Science:

• Nephrology
• Molecular Biology
• Developmental Biology

Background:

• Wilms tumor gene 1 (WT-1) is crucial for kidney development and is downregulated in obstructive nephropathy, leading to apoptosis.
• A functional interaction exists between WT-1 and inducible nitric oxide synthase (iNOS).
• Rosuvastatin has been shown to prevent apoptosis by increasing nitric oxide (NO) bioavailability and Hsp70 expression after neonatal ureteral obstruction.

Purpose of the Study:

• To investigate the role of a nitric oxide/Hsp70 interaction in regulating WT-1 mRNA expression following ureteral obstruction.
• To determine if rosuvastatin's protective effects against apoptosis in obstructive nephropathy are mediated by modulating WT-1 expression via NO and Hsp70.

Main Methods:

• Neonatal rats with experimental unilateral ureteral obstruction were treated with vehicle or rosuvastatin for 14 days.
• Kidney tissues were analyzed for WT-1, iNOS, Hsp70, Bax, and Bcl-2 expression, as well as apoptosis.
• In vitro studies using MDCK cells and in vivo experiments with NO modulators were conducted to confirm findings.

Main Results:

• Obstructed kidneys showed decreased NO, iNOS, Hsp70, and WT-1 expression, increased apoptosis, and a higher Bax/Bcl-2 ratio.
• Rosuvastatin treatment upregulated iNOS, Hsp70, and WT-1 mRNA in obstructed kidneys, concurrently reducing apoptosis.
• NO modulated Hsp70 and WT-1 mRNA expression in MDCK cells, and in vivo NO modulation supported the association between WT-1 expression and NO levels.

Conclusions:

• WT-1 mRNA expression is closely associated with nitric oxide levels.
• Rosuvastatin may enhance WT-1 mRNA expression by increasing renal NO bioavailability.
• This NO-mediated modulation of WT-1 and Hsp70 interaction likely prevents neonatal obstruction-induced apoptosis.