Roelofs M, Faggian L, Pampinella F, Paulon T, Franch R, Chiavegato A, Sartore S
Department of Biomedical Sciences, University of Padua, Italy.
Histochem J. 1998 Jun;30(6):393-404. doi: 10.1023/a:1003216124761.
In an attempt to identify the growth factors or cytokines involved in the serosal thickening that occurs in rabbit bladder subjected to partial outflow obstruction, the following growth factors--transforming growth factor beta1, platelet-derived growth factor, epidermal growth factor, granulocyte colony-stimulating factor and granulocyte-monocyte colony-stimulating factor--were delivered separately onto the serosal surface of the intact bladder via osmotic minipumps. The proliferative/differentiative cellular response of the rabbit bladder wall was evaluated by bromodeoxyuridine incorporation and immunofluorescence staining with a panel of monoclonal antibodies to cytoskeletal proteins (desmin, vimentin, keratins 8 and 18 and non-muscle myosin) and to smooth muscle (alpha-actin, myosin and SM22) proteins. Administration of the transforming growth factor, but not of the other growth factors/cytokines, was effective in inducing serosal thickening. Accumulating cells in this tissue were identified as myofibroblasts, i.e. cells showing a mixed fibroblast-smooth muscle cell differentiation profile. The phenotypic pattern of myofibroblasts changed in a time-dependent manner: 21 days after the growth factor delivery, small bundles of smooth muscle cells were found admixed with myofibroblasts, as occurs in the obstructed bladder. These 'ectopic' muscle structures displayed a variable 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 beta1 was delivered to fibroblasts of subcutaneous tissue. These findings suggest a tissue-specific role for this growth factor in the cellular conversion from myofibroblast to smooth muscle cells.
为了确定参与兔膀胱部分流出道梗阻时发生的浆膜增厚的生长因子或细胞因子，通过渗透微型泵将以下生长因子——转化生长因子β1、血小板衍生生长因子、表皮生长因子、粒细胞集落刺激因子和粒细胞 - 单核细胞集落刺激因子——分别输送到完整膀胱的浆膜表面。通过溴脱氧尿苷掺入以及用一组针对细胞骨架蛋白（结蛋白、波形蛋白、角蛋白8和18以及非肌肉肌球蛋白）和平滑肌（α - 肌动蛋白、肌球蛋白和SM22）蛋白的单克隆抗体进行免疫荧光染色，评估兔膀胱壁的增殖/分化细胞反应。给予转化生长因子可有效诱导浆膜增厚，而给予其他生长因子/细胞因子则无效。该组织中聚集的细胞被鉴定为肌成纤维细胞，即显示出成纤维细胞和平滑肌细胞混合分化特征的细胞。肌成纤维细胞的表型模式随时间变化：生长因子给药后21天，发现有小束平滑肌细胞与肌成纤维细胞混合，这与梗阻膀胱中的情况相同。这些“异位”肌肉结构表现出可变的增殖活性，并表达未成熟的平滑肌细胞表型。如果将转化生长因子β1输送到皮下组织的成纤维细胞，则无法实现完全向平滑肌细胞的细胞转化。这些发现表明该生长因子在从肌成纤维细胞到平滑肌细胞的细胞转化中具有组织特异性作用。
