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Impaired keratinocyte function on matrix metalloproteinase-1 (MMP-1) damaged collagen

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Abstract

Healing of superficial skin wounds depends on the proliferation and migration of keratinocytes at the wound margin. When human epidermal keratinocytes were incubated on polymerized type I collagen, they rapidly attached and spread. The cells underwent a proliferative response and, over the subsequent 6-day period, covered the collagen surface with a monolayer of cells. When keratinocytes were plated on collagen that had been fragmented by exposure to matrix metalloproteinase-1 (MMP-1, collagenase-1), the cells attached as readily as to intact collagen but spread more slowly and less completely. Growth was reduced by approximately 50%. Instead of covering the collagen surface, the keratinocytes remained localized to the site of attachment. Keratinocytes on fragmented collagen expressed a more differentiated phenotype as indicated by a higher level of surface E-cadherin. Based on these findings, we suggest that damage to the underlying collagenous matrix may impede efficient keratinocyte function and retard wound closure.

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Acknowledgments

This study was supported in part by grants GM077724 and GM080779 from the United Stated Public Health Service.

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Correspondence to James Varani.

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Varani, J., Perone, P., Deming, M.O. et al. Impaired keratinocyte function on matrix metalloproteinase-1 (MMP-1) damaged collagen. Arch Dermatol Res 301, 497–506 (2009). https://doi.org/10.1007/s00403-009-0948-4

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  • DOI: https://doi.org/10.1007/s00403-009-0948-4

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