Alterations of selected genes of the Wnt signal chain in rat kidneys with spontaneous congenital obstructive uropathy.

Objective: To determine the role of the Wnt signal cascade in the pathophysiology of congenital obstructive uropathy in rats, we assessed the expression patterns of selected genes.

Methods: Total cellular mRNA of complete obstructed, contralateral and healthy control kidneys of rats with hereditary, spontaneous congenital hydronephrosis at the age of 14 and 32days was extracted and pooled. mRNA expression was assessed by real-time reverse transcription-polymerase chain reaction.

Results: Significant (P<0.05) differences in gene expression levels of obstructed versus contralateral and control kidneys were evaluated. In 14-day-old animals, Wnt-4 expression was decreased. Secreted frizzled-related protein (sFRP-1, sFRP-2), beta-catenin and Jun N-terminal kinase (JNK) expression was increased. The gene expression of Wnt-7b, Friz-1, Friz-2, calcineurin and Wnt inhibitory factor-1 (WIF-1) was unaltered. In 32-day-old animals, Wnt-4, Wnt-7b, Friz-2, sFRP-1 and WIF-1 expression was increased, whereas levels of Friz-1, sFRP-2, beta-catenin, JNK and calcineurin were unaltered.

Conclusions: The results suggest an age-dependent role of Wnts in the pathophysiology of congenital renal obstruction in rats. Down-regulated Wnt signalling at the end of nephrogenesis in 14-day-old rats might indicate impaired tubulogenesis. Up-regulation of beta-catenin and JNK points to stressed cell-cell adhesion due to progressive hydronephrosis. Increased Wnt signalling in older animals probably contributes to interstitial fibrosis and tubular apoptosis. This study should be considered as a starting point to correlate in detail the observed alterations in gene expression with the pathophysiology of congenital obstructive uropathy.