Dysplasia, architectural derangement, extracellular matrix degradation and regulation of Tgf-ß3 within the interureteric muscle in children with vesicoureteral reflux

PURPOSE

The interureteric muscle represents an essential part of an adequate antireflux mechanism. Biopsies from children operated on for vesicoureteric reflux were investigated using morphological and immunohistochemical methods to evaluate smooth muscle configuration, potential muscle dysplasia and connective tissue changes in that area.

MATERIAL AND METHODS

Biopsies of the interureteric muscle were obtained from 22 ureterorenal units undergoing reflux surgery. Mean age of patients was 32 months, reflux grades III to V, respectively. Routine histological paraffin embedded sections were stained -actin to evaluate the presence,α with haematoxylin, eosin and smooth muscle allocation and morphological integrity of the interurerteric smooth muscle architecture. Indirect immunohistochemical methods were used to assess the extracellular matrix for collagen composition. Extracellular matrix involvement was assessed estimating transforming growth factor- ß III (TGF-ß3) expression.

RESULTS

All biopsies showed different grades of muscle atrophy and degradation. In these smooth muscle tissue lacking regions, disordered fibre arrangement associated with a 2 to 3-fold increase in endomysial and perimysial connective tissue in particular collagen type III was observed. Increased mesenchymal cell proliferation in the degenerated tissue areas was associated with a significant TGF-ß3 expression of the surrounding muscle cells and correlated with organized collagen deposition.

CONCLUSIONS

Extracellular matrix remodelling with interstitial fibrosis of the longitudinal muscle sheath of the ureterovesical junction may be mediated through upregulation of TGF-ß3. Diminution or even complete loss of contractile elements of the interureteric muscle in children with congenital vesicoureteral reflux is obviously associated with an inadequate antireflux mechanism of the vesicoureteral junction.

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