Adherence junctions and cadherin-11 in normal and overactive human detrusor smooth muscle cells

Abstract

PURPOSE: We investigated whether analysis of adherence junctions in human detrusor could be used as a diagnostic tool to determine detrusor overactivity. MATERIALS AND METHODS: We characterized the protein composition of adherence junctions in the human bladder using cadherin-11 since our group previously found that cadherin-11 could be an integral structural protein of adherence junctions. We obtained a total of 46 biopsies from 23 patients categorized into 4 groups, including 5 who were normal, and 6 each with neurogenic disease with detrusor overactivity, bladder outlet obstruction with detrusor overactivity and idiopathic detrusor overactivity. Specimens were processed to study cadherin-11 expression using combined immunohistochemical and immunogold electron microscopy techniques. Cadherin-11 expression was semiquantitatively analyzed and correlated to muscle fascicle structure and collagen in the extracellular spaces. RESULTS: Immunogold labeling showed highly specific cadherin-11 expression at adherence junctions in detrusor smooth muscle cells. During immunohistochemical staining a wide variety of cadherin-11 expression and fascicle structure was found in the same specimen. No correlation was noted between detrusor overactivity and cadherin-11 expression. However, cadherin-11 seemed to be down-regulated with intercellular space widening and collagenosis. CONCLUSIONS: Cadherin-11 is an integral structural protein of the adherence junction. Defects in the overactive detrusor are highly punctate. Quantitative analysis of adherence junctions using biopsy cannot replace urodynamic evaluation as a predictor of detrusor overactivity in the human bladder.