Extracellular Matrix Degradation and Reduced Neural Density in Children With Intrinsic Ureteropelvic Junction Obstruction

Abstract

To investigate the extracellular matrix microenvironment and nerve supply of ureteropelvic junctions (UPJs) in children with intrinsic UPJ obstruction. Congenital UPJ obstruction is the most common cause of neonatal hydronephrosis. Although many studies investigating the molecular changes within this segment have been performed, the underlying mechanisms of UPJ obstruction are still unclear. Specimens were obtained from 21 children with a mean age of 103.2 months undergoing dismembered pyeloplasty. Control samples included 9 archival specimens from age-matched children without any history of urologic disease. Paraffin-embedded sections were immunostained to detect matrix metalloproteinase 2 (MMP-2), tenascin C (TN-C), and S-100 (for the neuronal supply). Expression patterns were investigated using semiquantitative high-power field magnification analyses, and the MMP-2 and TN-C immunoreactivity were scored. Differences between the 2 groups were examined statistically. All UPJ specimens displayed a resolved muscular coat and replacement of smooth muscle cells by connective tissue. The degree of MMP-2 expression representing matrix turnover was statistically significantly elevated. Similarly, TN-C expression was found to be higher in obstructed specimens. Additionally, the mean S-100 staining was lower than in controls. Although S-100-positive nerve-fibers were more predominant in the adventitia with minimal submucosal and absent intramuscular staining in patient specimens, they were abundant in both adventitia and submucosa with minimal intramuscular staining in the controls. In intrinsic UPJ obstruction samples, a dissolved smooth muscular coat and an overexpression of extracellular matrix proteins, together with depleted nerve supply, was demonstrable.