By interfering with renal growth and development, congenital urinary tract obstruction constitutes one of the most important causes of renal failure in infants and children.
Obstructive nephropathy is also a significant cause of renal insufficency in the adult.
The phenotypic changes include altered expression of growth factors, loss of polarity, expression of mesenchymal markers, and detachment from the basement membrane. Apoptosis of tubular cells is markedly increased, contributing to tubular atrophy, while interstitial fibroblasts undergo proliferation and myofibroblast transformation, leading to progressive interstitial fibrosis. To control for internephron heterogeneity, single nephrons are obstructed by micropuncture. In addition, we are investigating factors regulating tubular cell phenotype and apoptosis. By elucidating the mechanisms by which the RTE cell regulates the response to UUO, the proposed studies may lead to new interventions to avert progression of renal insufficiency in patients with obstructive nephropathy.