1454 Identification of Fetuin A as a potential modulator of scar formation

Abstract

Wound healing generally leads to scarring in mature skin, but wounds created at early stages of development heal scarlessly. The exact mechanisms leading to scarless healing are not fully understood, but unique characteristics of fetal fibroblasts are believed to be important. Dermal fibroblasts from embryonic day 15 (E15) skin, which heals scarlessly, and embryonic day 18 (E18) skin, which heals with a scar, were compared by proteomics. Fetuin A (Fet A), a protein that has been suggested to be involved in inflammation, was identified as one of the top three differentially expressed proteins. Since inflammation is strongly linked to scar formation and Fet A was more highly expressed in fibroblasts from scar-forming skin, we hypothesized that Fet A may play a role in scar formation. To examine the role of Fet A in fetal wound healing, Fet A protein levels were first confirmed to be higher in E18 fibroblasts compared to E15 fibroblasts by Western blot. The ability of Fet A to induce scar formation was then tested by injecting recombinant Fet A into E15 fetal wounds, which normally heal without a scar. Injection of Fet A into E15 wounds caused the formation of a scar compared to control wounds, which healed scarlessly. The effects of Fet A on fibroblasts were also examined. Treatment of cultured fibroblasts from collagen-GFP reporter mice with Fet A resulted in a significant increase in GFP fluorescence, a readout of collagen expression, compared to untreated controls. These data suggest that Fet A may promote collagen production and scar formation. Further studies are being performed to dissect potential signaling mechanisms and to compare scar formation in wild-type and Fet A knockout mice.