Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing
Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing
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DOI：
10.1242/jcs.02346
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发表时间：
2005-06-01
影响因子：
4
通讯作者：
Hashimoto, K
中科院分区：
文献类型：
--
作者：
Shirakata, Y;Kimura, R;Hashimoto, K
表皮生长因子 (EGF) 家族的成员是参与皮肤伤口愈合过程中上皮化的最重要的生长因子。肝素结合 EGF 样生长因子 (HB-EGF) 是 EGF 家族的成员，被认为在皮肤伤口愈合中发挥重要作用。为了研究 HB-EGF 在皮肤伤口愈合中的体内功能，我们使用 Cre/loxP 技术结合角蛋白 5 启动子生成了角质形成细胞特异性 HB-EGF 缺陷小鼠。伤口愈合研究表明，角质形成细胞特异性 HB-EGF 缺陷小鼠的伤口闭合明显受损。 HB-EGF mRNA 在迁移的表皮边缘上调，但细胞生长没有改变。在 EGF 家族的成员中，HB-EGF mRNA 表达由于体外刮擦而被诱导得最快且最显着。综合起来，这些发现首次清楚地证明，HB-EGF 是体内皮肤伤口愈合中参与上皮化的主要生长因子，并且它通过加速角质形成细胞迁移而不是增殖来发挥作用。
Members of the epidermal growth factor (EGF) family are the most important growth factors involved in epithelialization during cutaneous wound healing. Heparin-binding EGF-like growth factor (HB-EGF), a member of the EGF family, is thought to play an important role in skin wound healing. To investigate the in vivo function of HB-EGF in skin wound healing, we generated keratinocyte-specific HB-EGF-deficient mice using Cre/loxP technology in combination with the keratin 5 promoter. Studies of wound healing revealed that wound closure was markedly impaired in keratinocyte-specific HB-EGF-deficient mice. HB-EGF mRNA was upregulated at the migrating epidermal edge, although cell growth was not altered. Of the members of the EGF family, HB-EGF mRNA expression was induced the most rapidly and dramatically as a result of scraping in vitro. Combined, these findings clearly demonstrate, for the first time, that HB-EGF is the predominant growth factor involved in epithelialization in skin wound healing in vivo and that it functions by accelerating keratinocyte migration, rather than proliferation.