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Published online 20 October 2003. doi:10.1083/jcb.200305032
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© The Rockefeller University Press, 0021-9525/2003/10/327 $8.00
The Journal of Cell Biology, Volume 163, Number 2, 327-337


Article

Loss of keratin 6 (K6) proteins reveals a function for intermediate filaments during wound repair

Pauline Wong1 and Pierre A. Coulombe1,2

1 Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205
2 Department of Dermatology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205

Address correspondence to Pierre A. Coulombe, Dept. of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe St., Baltimore, MD 21205. Tel.: (410) 614-0510. Fax: (410) 614-7567. email: coulombe{at}jhmi.edu

The ability to heal wounds is vital to all organisms. In mammalian tissues, alterations in intermediate filament (IF) gene expression represent an early reaction of cells surviving injury. We investigated the role of keratin IFs during the epithelialization of skin wounds using a keratin 6{alpha} and 6ß (K6{alpha}/K6ß)-null mouse model. In skin explant culture, null keratinocytes exhibit an enhanced epithelialization potential due to increased migration. The extent of the phenotype is strain dependent, and is accompanied by alterations in keratin IF and F-actin organization. However, in wounded skin in vivo, null keratinocytes rupture as they attempt to migrate under the blood clot. Fragility of the K6{alpha}/K6ß-null epidermis is confirmed when applying trauma to chemically treated skin. We propose that the alterations in IF gene expression after tissue injury foster a compromise between the need to display the cellular pliability necessary for timely migration and the requirement for resilience sufficient to withstand the rigors of a wound site.

Key Words: mouse skin grafting; keratin; skin; injury; wound healing; migration


Abbreviations used in this paper: CNS, central nervous system; GFAP, glial fibrillary acidic protein; H&E, hematoxylin and eosin; IF, intermediate filament.


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