Dermal wound healing is subject to redox control
Dermal wound healing is subject to redox control
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DOI：
10.1016/j.ymthe.2005.07.684
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发表时间：
2006-01-01
影响因子：
12.4
通讯作者：
Sen, CK
中科院分区：
文献类型：
--
作者：
Roy, S;Khanna, S;Sen, CK
以前我们报道过的体外证据表明H2O2可能通过诱导人角质形成细胞中VEGF的表达来支持伤口愈合（C. K. Sen等，2002，J. Biol.）。化学，277,33284-33290)。在这里，我们在体内测试H2O2在调节伤口愈合中的意义。使用亨特-席林圆柱体方法，我们提出了伤口部位含有微摩尔浓度H2O2的第一个证据。在伤口部位，低浓度的H2O2支持愈合过程，特别是在内源性H2O2生成受损的p47(phox) -和mcp -1缺陷小鼠中。较高剂量的H2O2对愈合有不利影响。在低浓度下，H2O2促进了体内伤口血管生成。H2O2诱导体内创口边缘组织和人皮肤微血管内皮细胞中FAK磷酸化。H2O2诱导FAK位点特异性（Tyr-925和Tyr-861）磷酸化。其他位点，包括Tyr-397自磷酸化位点，对H2O2不敏感。腺病毒基因传递过氧化氢酶损伤伤口血管生成和愈合。过氧化氢酶过表达减缓了组织重塑，其证据是增生性上皮区域更不完全变窄和不完全瘢痕形成。综上所述，这项工作首次提出了体内证据，表明影响伤口氧化还原环境的策略可能对愈合结果有影响。
Previously we have reported in vitro evidence suggesting that that H2O2 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 H2O2 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 H2O2. At the wound site, low concentrations of H2O2 supported the healing process, especially in p47(phox) - and MCP-1-deficient mice in which endogenous H2O2 generation is impaired. Higher doses of H2O2 adversely influenced healing. At low concentrations, H2O2 facilitated wound angiogenesis in vivo. H2O2 induced FAK phosphorylation both in wound-edge tissue in vivo and in human dermal microvascular endothelial cells. H2O2 induced site-specific (Tyr-925 and Tyr-861) phosphorylation of FAK. Other sites, including the Tyr-397 autophosphorylation site, were insensitive to H2O2. 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.