MYOFIBROBLAST-DERIVED SMOOTH-MUSCLE CELLS DURING REMODELING OF RABBITURINARY-BLADDER WALL-INDUCED BY PARTIAL OUTFLOW OBSTRUCTION

BACKGROUND: Fibrosis of serosa, along with smooth muscle (SM) cell hyp ertrophy, has been shown to occur in the rabbit bladder after partial outflow obstruction. Identification of cells involved in the serosal t hickening can be of primary interest to elucidate the functional chang es that this organ undergoes. EXPERIMENTAL DESIGN: Cytoskeletal protei n composition of cells present in the thickened serosa at different ti mes from the onset of obstruction (7, 15, 30 and 60 days) was evaluate d. This was accomplished by means of a panel of monoclonal antibodies specific for a number of differentiation markers of mesenchymal cells (vimentin, desmin, alpha-actin of SM type, nonmuscle (NM) and SM myosi ns), and by immunocytochemical and immunochemical techniques. RESULTS: The immunocytochemical study revealed that cells in serosal thickenin g follow a two-step maturation process from pre-existing vimentin-posi tive cells. In the first time period (7 to 15 days of obstruction), th ese cells predominantly achieved an immunophenotype corresponding to t hat of a specific myofibroblast subtype (i.e., containing vimentin, NM myosin, and SM alpha-actin). After 30 days from the onset of obstruct ion, the cytoskeletal protein content of serosa cells, as also reveale d by Western blotting experiments, shifted towards that of fetal-type SM cells (i.e., presence of vimentin, NM myosin, SM a-actin, and SM my osin isoforms). Distribution of vimentin, desmin, SM alpha-actin, and SM myosin in tissue culture as well as the ultrastructure in vivo very closely resembled that of SM cells. Bromodeoxyuridine incorporation s tudies indicated that cells accumulated in the serosa of obstructed bl adders did not derive, at least initially, from SM cells of the detrus or muscle. CONCLUSIONS: These findings are consistent with the existen ce of a differentiation process in which resident mesenchymal cells of bladder serosa may transform to myofibroblasts and, subsequently, in fetal-type SM cells during experimental outflow obstruction.