Chronic stretch-induced tissue expansion is accompanied by increased expression of several growth factors and receptors that may contribute to cell proliferation and tissue remodeling required for expansion. In smooth muscle cells, these proteins include members of the transforming growth factor, epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor, and nerve growth factor families (9-14). In bladder smooth muscle cells, mechanical stretch increased expression of heparin-binding epidermal growth factor-like growth factor and one of its receptors, ErbB1, resulting in inhibition of apoptosis (10). Stretch also induced production of nerve growth factor by urinary tract smooth muscle cells (11), and lower urinary tract obstruction induced hypertrophy of bladder afferent and efferent neurons that appeared to require increased nerve growth factor expression (12). The latter finding supports the hypothesis that obstruction-induced tissue expansion induces remodeling of the neural networks.

Stretch-induced tissue expansion also involves extracellular matrix production, which is required for stretch-induced cell proliferation (9). In vascular smooth muscle cells, mechanical strain-induced fibroblast growth and extracellular matrix production were accompanied by increased expression of transforming growth factor-p1 and inhibited by a transforming growth factor-p1 neutralizing antibody (13). Rapid tissue expansion also may injure ureteral tissue more seriously than slow expansion, with associated ischemia and inflammation. transforming growth factor-p1 may be the main regulating factor for both the repair process and inflammatory response. We observed two to threefold increases in transforming growth factor-p2 expression in porcine chronic expanded versus native ureteral tissues (30).

Chronic tissue expansion has also been shown to induce angiogenesis, with associated ischemia, which in turn can stimulate production of vascular endothelial growth factor (14). Ischemia induced by tissue expansion may also determine the degree of any ensuing fibrosis. In our preliminary study, no change in vascular endothelial growth factor expression was observed in the expanded ureteral tissue (30). It should be noted that all of the above-cited literature regarding mechanisms of stretch-induced tissue remodeling pertains to cutaneous (skin) tissue expansion on cultured cells.

The methodology of visceral tissue expansion in the genitourinary system has yet to be refined to a place where it can have a real practical use by urologists, to the extent that skin expansion has become an accepted part of plastic reconstructive surgery.

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