Loss of Keratin 6 (K6) Proteins Reveals a Function for Intermediate Filaments during Wound Repair

• Published in: The Journal of cell biology Vol. 163; no. 2; pp. 327 - 337
• Main Authors: Wong, Pauline, Coulombe, Pierre A.
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 27.10.2003; The Rockefeller University Press
• Subjects: Actins; Animals; Cell Movement - physiology; Cells, Cultured; Cellular biology; Epidermis; Epithelial cells; Gene Expression; Gene expression regulation; Injuries; Intermediate filaments; Intermediate Filaments - metabolism; Keratinocytes; Keratinocytes - cytology; Keratinocytes - physiology; Keratins; Keratins - genetics; Keratins - metabolism; Keratins - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Nude; Mutation; Organ Culture Techniques; Physical trauma; Proteins; Skin; Skin - cytology; Skin - metabolism; Transplantation, Homologous; Transplants; Wound Healing - physiology
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200305032

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 6α and 6β (K6α/K6β)-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 K6α/K6β-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.