부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ymthe.2005.07.684 Byline: Sashwati Roy (1), Savita Khanna (1), Kishore Nallu (1), Thomas K. Hunt (2), Chandan K. Sen (1) Keywords: trauma; hydrogen peroxide; redox signaling; oxygen Abstract: Previously we have reported in vitro evidence suggesting that that H.sub.2O.sub.2 may support wound healing by inducing VEGF expression in human keratinocytes (C. K. Sen et al., 2002, J. Biol. Chem. 277, 33284-33290). Here, we test the significance of H.sub.2O.sub.2 in regulating wound healing in vivo. Using the Hunt-Schilling cylinder approach we present the first evidence that the wound site contains micromolar concentrations of H.sub.2O.sub.2. At the wound site, low concentrations of H.sub.2O.sub.2 supported the healing process, especially in p47.sup.phox- and MCP-1-deficient mice in which endogenous H.sub.2O.sub.2 generation is impaired. Higher doses of H.sub.2O.sub.2 adversely influenced healing. At low concentrations, H.sub.2O.sub.2 facilitated wound angiogenesis in vivo. H.sub.2O.sub.2 induced FAK phosphorylation both in wound-edge tissue in vivo and in human dermal microvascular endothelial cells. H.sub.2O.sub.2 induced site-specific (Tyr-925 and Tyr-861) phosphorylation of FAK. Other sites, including the Tyr-397 autophosphorylation site, were insensitive to H.sub.2O.sub.2. Adenoviral gene delivery of catalase impaired wound angiogenesis and closure. Catalase overexpression slowed tissue remodeling as evidenced by a more incomplete narrowing of the hyperproliferative epithelium region and incomplete eschar formation. Taken together, this work presents the first in vivo evidence indicating that strategies to influence the redox environment of the wound site may have a bearing on healing outcomes. Author Affiliation: (1) Laboratory of Molecular Medicine, Department of Surgery, Comprehensive Wound Center, Davis Heart & Lung Research Institute, The Ohio State University Medical Center, Columbus, OH 43210, USA (2) Department of Surgery, University of California at San Francisco, San Francisco, CA 94143, USA Article History: Received 13 April 2005; Revised 7 July 2005; Accepted 10 July 2005