Wnt Signaling Pathway Proteins in Scar, Hypertrophic Scar, and Keloid: Evidence for a Continuum?

Hypertrophic scars and keloids are fibroproliferative lesions characterized by excessive collagen deposition. It is unclear whether these entities represent distinct disorders or share a common pathogenesis and the molecular underpinnings of these lesions are poorly understood. Accumulating evidence suggests that the Wnt signaling pathway is a key regulator of wound healing. In this study, tissue microarray was used to evaluate the protein expression profile for Wnt3a, phosphorylated glycogen synthase kinase 3 alpha (pGSK-3 alpha), WNT1-inducible-signaling pathway protein 1 (WISP1), and WISP2 in normal skin, scars, hypertrophic scars, and keloids. Analysis revealed significantly increased fibroblast expression of pGSK-3 alpha in scars (27.2%), hypertrophic scars (30.4%), and keloids (57.3%) compared with normal skin (16.4%) (all differences statistically significant; P < 0.01). Analysis of WISP2 showed 94% of fibroblasts in normal skin expressing WISP2 and significantly decreased expression in scars (46.8%), hypertrophic scars (27.0%), and keloids (61.3%) (all differences statistically significant; P < 0.01). The parallel patterns of expression of pGSK-3 alpha and WISP2 in scars and hypertrophic scars and significantly increased expression in keloids may support the notion that keloids are a truly distinct fibrosing disorder and may provide further evidence for targeting the Wnt signaling pathway in the treatment of keloids.