Evidence That Fetuin-a Contributes To Cutaneous Scar Formation
Nicholas K. Pappa, Brian C. Wulff, Traci A. Wilgus.
Ohio State University, Columbus, OH, USA.
The formation of scar tissue is an unwanted consequence of successful healing in mature skin. Unfortunately, effective therapies to limit scar formation are lacking, so there is a need to better understand the mechanisms controlling this process. Comparing scarless and fibrotic fetal wounds is one strategy that has been used successfully to identify novel regulators of dermal scar formation. Our lab performed a proteomics study comparing dermal fibroblasts isolated from embryonic day 15 (E15) skin, which heals scarlessly, and embryonic day 18 (E18) skin, which heals with a scar. One of the top differentially expressed proteins was Fetuin-A (Fet-A), which was more abundant in E18 fibroblasts. Fet-A is a serum protein that modulates calcification. Studies have suggested that Fet-A is a ligand for toll-like receptor 4 and that it promotes inflammation. Given that inflammation typically stimulates scar formation and that Fet-A was more highly expressed in fibroblasts from scar-forming E18 skin, we hypothesized that Fet-A may play a role in scar formation. In vitro studies using cultured murine fibroblasts showed that treatment with Fet A significantly increased collagen production compared to untreated controls. A role for Fet-A in scar tissue production was also tested in vivo using two different murine models. First, recombinant Fet-A was injected into E15 fetal wounds, which normally heal without a scar. A significant number of E15 wounds injected with Fet-A healed with a scar, whereas control wounds that were not exposed to Fet-A healed scarlessly. In addition, scar formation was compared in adult wild-type and Fet-A knockout mice after incisional wounding. Scar area was significantly reduced in Fet-A knockout mice compared to wild-type mice 14 days post-wounding. Together, the data suggest that Fet-A may promote collagen production and scar formation. Further studies are now being conducted to evaluate mechanisms by which Fet-A promotes scar formation.
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