Smooth Muscle Cell Apoptosis and Defective Neural Development in Congenital Ureteropelvic Junction Obstruction

Abstract

We assessed the smooth muscle cell apoptosis along with changes in cellular and extracellular components of the ureteropelvic junction in 23 patients with unilateral obstruction and compared them with 25 autopsies from ureteropelvic junction regions of age matched cadavers. Tissue specimens obtained from pyeloplasty were divided into 3 sections-renal pelvis above the obstruction, obstructed ureteropelvic junction and ureter below the obstructed region. For the control group the normal ureteropelvic junctions of age matched infants were autopsied. In paraffin embedded sections we determined myocyte apoptosis index (using TUNEL assay), and the amount of muscular components and nerve terminals (using image analysis techniques after immunohistochemical staining). The collagen and elastin fibers were specifically stained for evaluation of changes in extracellular matrix. Smooth muscle cell apoptosis index was significantly increased at the site of ureteropelvic junction obstruction (5.68 +/- 0.18) compared to normal autopsied ureteropelvic junctions (3.60 +/- 0.11) and 2 other sections of obstructed ureteropelvic junction complex (renal pelvis 4.73 +/- 0.16, and ureter 3.97 +/- 0.16). The number of nerve terminals and the percentage of muscular component were significantly lower at the obstructed segments of affected patients compared to normal ureteropelvic junctions. Meanwhile, collagen fibers formed a significantly higher proportion of ureteral wall at the site of obstruction. Interestingly, there was negative correlation between myocyte apoptosis indices and number of nerve endings as well as amount of muscular components at the site of ureteropelvic junction obstruction. However, positive correlations were found between smooth muscle cell apoptosis and the percentage of collagen and elastin fibers. Our findings suggest an important role for myocyte apoptosis and defective neural development in the pathogenesis of congenital ureteropelvic junction obstruction that could pave the road for the emergence of new therapeutic modalities.