ALTERED SMOOTH MUSCLE CELL – EXTRACELLULAR MATRIX INTERACTION IN CONGENITAL VESICO-URETERAL JUNCTION OBSTRUCTION

Introduction and Objectives The pathophysiology of vesico-ureteric junction obstruction (VUJO) is still unclear. An abnormal myocyte apoptosis and a significant reduction of neural elements has been described in VUJO. Cholinergic innervations of the upper urinary tract might play a crucial role in the transmission of ureteral peristalsis. Agrins are involved in achetylcholine receptors aggregation during synaptogenesis. Integrins are transmembrane proteins involved in cell differentiation, interaction of the cells with the extracellular matrix, maintenance of tissue integrity and have a main function in embryological development. Aim was to investigate the expression of neural and non-neural agrin and á7-A, á7-B, â1-A and â1-D integrins in obstructed ureteral endings of children affected by VUJO Methods Tissue specimens obtained from ten ureteral reimplants, performed for congenital VUJO, were divided into two parts, distal restricted ureter and dilated ureter above the obstruction. For control group, eight autoptic unaffected distal ureters of matched-aged infants were used. Specimens were exanimated using anti-neural and non-neural agrin, anti-â1-D, -â1-A, -á7-B and -á7-A integrin antibodies. Sections were observed using a confocal laser scanning microscopy. Results A significant loss of agrins, â1-D and á7-B integrins were detected in restricted ureter coupled to an enhancement of á7-A and â1-A integrins. Differently, a similar expression of agrins, â1-D and á7-B integrins were documented in dilated and control ureters, while a low expression of â1-A and á7-A integrins occurred. Conclusions The changes in agrin expression could contribute to altered innervations and function of smooth muscle cells in hypoperistaltic segment in VUJO. Moreover, we observed an alternatively spliced isoform of both á and â integrin subunits. It has been shown that cell matrix adhesion via integrins protects from apoptosis, allowing cell survival. Expression of â1-A and á7-A integrins is developmentally regulated during embryogenesis and a delayed rearrangement of cytoskeleton of SMC in VUJO might be linked to a post-natal splicing from á7A and â1A to, respectively, á7B and â1D integrins. These data perfectly are in accordance with the clinical evidence of a possible post-natal healing of congenital VUJO. Our data suggest that a main anomaly in VUJO might be attributed to an abnormal expression of agrins and to an alteration of smooth muscle cell cytoskeleton, promoting an impairment of contractile function.