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-β) isoforms, TGF-β₁ and TGF-β₂, in the proliferative, involutional, and residual stages of Dupuytren's disease. The effect of TGF-β on myofibroblast proliferation was also studied using explant cultures from Dupuytren's nodules in the proliferative or involutional stage. TGF-β₁, TGF-β₂ 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-β₁ showed an intense intracellular marking pattern associated with fibroblasts, myofibroblasts, and capillary endothelial cells in all Dupuytren's samples, regardless of disease stage. TGF-β₂ showed an intense intracellular localization within myofibroblasts in the proliferative and involutional stages. Fibroblasts in the residual stage did not contain TGF-β₂. Neither isoform was present in the extracellular matrix. Results of cell culture indicate that compared with control myofibroblasts, the addition of TGF- β₁, TGF-β₂ and TGF-β₁ + β₂ had significant effects on myofibroblast proliferation, especially at higher plating densities. However, TGF-β₂ had the most significant proliferative effect.