Upregulation of the Wnt/β-catenin pathway induced by transforming growth factor-β in hypertrophic scars and keloids

Abstract

Hypertrophic scars and keloids represent a dysregulated response to cutaneous wounds, which results in an excessive deposition of collagen. Transforming growth factor-β (TGF-β) is the key regulator in the pathogenesis of fibrosis. Accumulating evidence suggests that Wnt signalling and its effector β-catenin also play an important role in wound healing. The role of Wnt/β-catenin signalling in TGF-β induced collagen deposition in hypertrophic scars and keloids was studied. Transcriptional assays and Western blotting was performed using fibroblast cell lines established from normal skin and hypertrophic scar tissue. Immunohistochemical studies were performed using scar tissues. We provide evidence that TGF-β induces activation of β-catenin mediated transcription in human dermal fibroblasts via the Smad3 and p38 MAPK pathways. Immunohistochemical studies demonstrated that β-catenin protein levels are elevated in hypertrophic scar and keloid tissues. This finding may be relevant to the pathogenesis of hypertrophic scars and keloids. © 2006 Acta Demato-Venereologica.