EPIDERMAL GROWTH-FACTOR (EGF) PROMOTES HUMAN KERATINOCYTE LOCOMOTION ON COLLAGEN BY INCREASING THE ALPHA-2 INTEGRIN SUBUNIT
EPIDERMAL GROWTH-FACTOR (EGF) PROMOTES HUMAN KERATINOCYTE LOCOMOTION ON COLLAGEN BY INCREASING THE ALPHA-2 INTEGRIN SUBUNIT
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DOI：
10.1006/excr.1993.1304
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发表时间：
1993-12-01
影响因子：
3.7
通讯作者：
KIM, JP
中科院分区：
文献类型：
--
作者：
CHEN, JD;ZHANG, K;KIM, JP
人角质形成细胞穿过伤口床的迁移是皮肤伤口再上皮化的早期和关键事件。表皮生长因子（EGF）已被证明可以加速新鲜的，局部应用时，分层皮肤伤口的愈合。这种加速愈合的机制仍然未知。使用的测定，直接评估人角质形成细胞运动，而不混淆细胞增殖的可能性，我们研究了表皮生长因子对人角质形成细胞运动的影响。重组表皮生长因子（rEGF）和转化生长因子-α（TGF-α）均能促进人角质形成细胞在胶原或纤连蛋白结缔组织基质（创面床的重要成分）上的运动。其他生长因子的研究没有提高角质形成细胞迁移。用特异性抗体阻断角质形成细胞表面EGF/TGF-α受体可抑制rEGF和TGF-α对角质形成细胞运动的刺激。在rEGF或TGF-α存在下，角质形成细胞在I型胶原上迁移的流式细胞术分析显示角质形成细胞表面α2整合素亚基的表达增加。α2β1整联蛋白介导I型和IV型胶原上的角质形成细胞迁移，通过增加培养基中rEGF的浓度，可以部分克服通过α2β1整联蛋白的抗体阻断对迁移的抑制。我们的研究表明，通过调节整合素表达的角质形成细胞运动的生长独立的刺激可能是EGF加速人类皮肤伤口的上皮再生的一种机制。
The migration of human keratinocytes across the wound bed is an early and critical event in the reepithelialization of cutaneous wounds. Epidermal growth factor (EGF) has been shown to accelerate the healing of fresh, split-thickness cutaneous wounds when applied topically. The mechanism(s) by which this accelerated healing occurs remains unknown. Using an assay that directly evaluates human keratinocyte locomotion without confounding the possibility of cell proliferation, we examined the influence of EGF on human keratinocyte motility. Both recombinant epidermal growth factor (rEGF) and transforming growth factor-α (TGF-α) promoted human keratinocyte locomotion when the cells were apposed to connective tissue matrices of collagen or fibronectin, important components of the wound bed. Other growth factors studied did not enhance keratinocyte migration. Blocking the EGF/TGF-α receptor on the cell surface of keratinocytes with specific antibody inhibited the stimulation of keratinocyte locomotion by rEGF and TGF-α. Flow cytometry analysis of keratinocytes migrating on type I collagen in the presence of rEGF or TGF-α revealed increased expression of the α2 integrin subunit on the keratinocyte surface. The α2β1 integrin mediates keratinocyte migration on collagens type I and IV, and inhibition of migration via antibody blockade of the α2β1 integrin can be partially overcome by increasing the concentration of rEGF present in the medium. Our study demonstrates that the growth-independent stimulation of keratinocyte locomotion via regulation of integrin expression may be one mechanism by which EGF accelerates the reepithelialization of human cutaneous wounds.