Submitted on July 21, 2006
Accepted on October 24, 2006
PAX2 is reactivated in urinary tract obstruction and partially protects collecting duct cells from programmed cell death
Tiffany Cohen1, Oleg Loutochin2, Moamen Amin2, John-Paul Capolicchio3, Paul Goodyer4*, and Roman Jednak2
1 Pediatrics, McGill University, Montreal, Canada
2 Urology, McGill University, Montreal, Canada
3 Urology, McGil University, Montreal, Canada
4 Division of Pediatric Nephrology, Montreal Children's Hospital, Montreal, Canada
* To whom correspondence should be addressed. E-mail: paul.goodyer{at}mcgill.ca.
Obstruction of the urinary tract activates apoptotic pathways in collecting duct cells and leads to loss of renal parenchyma prior to surgical intervention. It has been suggested that developmental pathways may be reactivated to offset acute organ damage. One such molecule, PAX2, is expressed throughout the fetal collecting duct and was recently shown to suppress apoptosis during kidney development. We hypothesized that acute unilateral urinary tract obstruction (UUO) reactivates PAX2 expression in the mature kidney and partially suppresses apoptosis. If so, animals with PAX2 mutations should have increased susceptibility to parenchymal damage. Wildtype and heterozygous Pax2 mutant C3H/Pax21Neu mice underwent unilateral ureteric ligation or sham operation at 6 weeks of age; kidneys were examined after 5, 10 and 15 days. Whereas PAX2 protein levels fell to low levels in the first weeks of life, it was sharply reactivated by Day 10 in collecting duct cells of wildtype but not in Pax21Neu mutant mice with UUO. Wildtype mice with UUO had marked TUNEL and cleaved spectrin staining in tubular cells and reduced kidney weight after 10-15 days. Mutant mice had exaggerated increases in markers of apoptosis and exaggerated loss of renal parenchymal in the obstructed kidney. These observations suggest that PAX2 is rapidly reactivated in UUO and that mice with genetically limited PAX2 expression have heightened susceptibility to apoptosis.
