A TGF-β1-dependent autocrine loop regulates the structure of focal adhesions in hypertrophic scar fibroblasts

larger focal adhesions than do normal dermal fibroblasts and these focal adhesions attach to alpha SMCA-rich stress fibers. Following severe traumatic or thermal injury to the dermis, hypertrophic scars (HTSs) often develop and these scar fibroblasts (HTSFs) express alpha SMCA persistently. We now report that HTSFs stably display large focal adhesions as a consequence of both the autocrine production and activation of transforming growth factor beta 1 (TGF-beta 1). We also observe that myofibroblasts elaborating larger focal adhesions adhere more tightly to fibronectin. Conditioned medium from HTSFs induces focal adhesion growth in normal fibroblasts and this is blocked by pre-incubation with a soluble TGF-beta 1 receptor mimetic. Human foreskin fibroblasts transduced with a retrovirus encoding active TGF-beta 1 elaborate large focal adhesions, whereas fibroblasts overexpressing normal, latent TGF-beta 1 do not. We conclude that the large focal adhesions found in pathogenic myofibroblasts arise through an autocrine loop involving the production and activation of TGF-beta 1; these adhesions likely mediate both tighter adhesion to wound matrix and the exuberant wound contraction observed in pathogenic scars.