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Developmental transcription factor slug is required for effective re‐epithelialization by adult keratinocytes
Author(s) -
Savagner Pierre,
Kusewitt Donna F.,
Carver Ethan A.,
Magnino Fabrice,
Choi Chagsun,
Gridley Thomas,
Hudson Laurie G.
Publication year - 2005
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20188
Subject(s) - slug , microbiology and biotechnology , keratinocyte , wound healing , biology , transcription factor , keratinocyte growth factor , cell migration , epithelial–mesenchymal transition , cell , in vitro , immunology , cancer research , growth factor , downregulation and upregulation , receptor , genetics , biochemistry , gene
During re‐epithelialization of cutaneous wounds, keratinocytes recapitulate several aspects of the embryonic process of epithelial‐mesenchymal transition (EMT), including migratory activity and reduced intercellular adhesion. The transcription factor Slug modulates EMT in the embryo and controls desmosome number in adult epithelial cells, therefore, we investigated Slug expression and function during cutaneous wound re‐epithelialization. Slug expression was elevated in keratinocytes bordering cutaneous wounds in mice in vivo, in keratinocytes migrating from mouse skin explants ex vivo, and in human keratinocytes at wound margins in vitro. Expression of the related transcription factor Snail was not significantly modulated in keratinocytes during re‐epithelialization in vitro. Epithelial cell outgrowth from skin explants of Slug knockout mice was severely compromised, indicating a critical role for Slug in epithelial keratinocyte migration. Overexpression of Slug in cultured human keratinocytes caused increased cell spreading and desmosomal disruption, both of which were most pronounced at wound margins. Furthermore, in vitro wound healing was markedly accelerated in keratinocytes that ectopically expressed Slug. Taken together, these findings suggest that Slug plays an important role during wound re‐epithelialization in adult skin and indicate that Slug controls some aspects of epithleial cell behavior in adult tissues as well as during embryonic development. © 2004 Wiley‐Liss, Inc.