The Role of Transforming Growth Factor Beta in Dupuytren's Disease

This study was undertaken to mark immunologically intracellular and extracellular sites of two common transforming growth factor beta (TGF-beta) isoforms, TGF-beta1 and TGF-beta2, in the proliferative, involutional, and residual stages of Dupuytren's disease. The effect of TGF-beta on myofibroblast proliferation was also studied using explant cultures from Dupuytren's nodules in the proliferative or involutional stage. TGF-beta1, TGF-beta2 and the combination of both isoforms were studied at low and high myofibroblast plating densities to simulate respectively proliferative or involutional disease stage conditions. Our results indicate that TGF-beta1 showed an intense intracellular marking pattern associated with fibroblasts, myofibroblasts, and capillary endothelial cells in all Dupuytren's samples, regardless of disease stage. TGF-beta2 showed an intense intracellular localization within myofibroblasts in the proliferative and involutional stages. Fibroblasts in the residual stage did not contain TGF-beta2. Neither isoform was present in the extracellular matrix. Results of cell culture indicate that compared with control myofibroblasts, the addition of TGF-beta1, TGF-beta2 and TGF-beta1 + beta2 had significant effects on myofibroblast proliferation, especially at higher plating densities. However, TGF-beta2 had the most significant proliferative effect.