TRANSFORMING-GROWTH-FACTOR BETA-1 INVOLVEMENT IN THE CONVERSION OF FIBROBLASTS TO SMOOTH-MUSCLE CELLS IN THE RABBIT BLADDER SEROSA

In an attempt to identify the growth factors or cytokines involved in the serosal thickening that occurs in rabbit bladder subjected to part ial outflow obstruction, the following growth factors - transforming g rowth factor beta 1, platelet-derived growth factor, epidermal growth factor, granulocyte colony-stimulating factor and granulocyte-monocyte colony stimulating factor - were delivered separately onto the serosa l surface of the intact bladder via osmotic minipumps. The proliferati ve/differentiative cellular response of the rabbit bladder wall was ev aluated by bromodeoxyuridine incorporation and immunofluorescence stai ning with a panel of monoclonal antibodies to cytoskeletal proteins (d esmin, vimentin, keratins 8 and 18 and non-muscle myosin) and to smoot h muscle (alpha-actin, myosin and SM22) proteins. Administration of th e transforming growth factor, but not of the other growth factors/cyto kines, was effective in inducing serosal thickening. Accumulating cell s in this tissue were identified as myofibroblasts, i.e. cells showing a mixed fibroblast-smooth muscle cell differentiation profile. The ph enotypic pattern of myofibroblasts changed in a time-dependent manner: 21 days after the growth factor delivery, small bundles of smooth mus cle cells were found admired with myofibroblasts, as occurs in the obs tructed bladder. These 'ectopic' muscle structures displayed a variabl e proliferating activity and expressed an immature smooth muscle cell phenotype. The complete cellular conversion to smooth muscle cells was not achieved if transforming growth factor beta 1 was delivered to fi broblasts of subcutaneous tissue. These findings suggest a tissue-spec ific role for this growth factor in the cellular conversion from myofi broblast to smooth muscle cells.