Figure 6
Schematic representation of perturbed TGF-β/Smad and mitogen-activated protein kinase signalling pathways in Dupuytren's fibroblasts. The TGF-β/Smad canonical Smad2/3 pathway and the noncanonical ERK1/2 mitogen-activated protein (MAP) kinase signalling pathways are depicted, as well as the PDGF-induced Ras/Raf/MEK/ERK1/2/MAP kinase pathway. TGF-β induces the production of PDGF and other growth factors. The symbols of corresponding downstream regulated genes are shown in italics. Inhibition by STI571, SB-431542 and PD98059 of the aberrantly overactivated signalling pathways in Dupuytren's fibroblasts is indicated. The mechanism by which BMP6 inhibits TGF-β expression and downstream responses is unclear. SB-431542 inhibits not only TGF-β/activin receptor-like kinase 5 (ALK5) signalling but also activin/ALK4 and nodal/ALK7 signalling. Our experiments do not rule out a role for these signalling pathways in Dupuytren's fibroblasts. Our data suggest that the TGF-β/Smad and PDGF/ERK MAP kinase pathways are targets for therapeutic intervention strategies to treat DD.