An Important Role for Protein Kinase C-δ in Human Keratinocyte Migration on Dermal Collagen

Migration of human keratinocytes plays a critical role in the re-epithelialization of human skin wounds, the process by which the wound bed is resurfaced and closed by keratinocytes as it forms a new epidermis. While the importance of ECM components and serum factors in the regulation of keratinocyt...

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Bibliographic Details
Published in:Experimental cell research 2002-02, Vol.273 (2), p.219-228
Main Authors: Li, Wei, Nadelman, Celina, Gratch, Noah S., Li, Weiquin, Chen, Mei, Kasahara, Nori, Woodley, David T.
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Cell Movement - drug effects
Cell Movement - physiology
Cells, Cultured
Collagen - metabolism
Dermis - cytology
Dermis - metabolism
Enzyme Inhibitors - pharmacology
Genetic Vectors - genetics
HIV-1 - genetics
Humans
Isoenzymes - antagonists & inhibitors
Isoenzymes - genetics
Isoenzymes - physiology
Keratinocytes - cytology
Keratinocytes - enzymology
Keratinocytes - physiology
Mice
Protein Kinase C - antagonists & inhibitors
Protein Kinase C - genetics
Protein Kinase C - physiology
Protein Kinase C-delta
Transduction, Genetic
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Summary:Migration of human keratinocytes plays a critical role in the re-epithelialization of human skin wounds, the process by which the wound bed is resurfaced and closed by keratinocytes as it forms a new epidermis. While the importance of ECM components and serum factors in the regulation of keratinocytes motility is well established, the intracellular signaling mechanisms remain fragmentary. In this study, we investigated the role of protein kinase Cδ (PKCδ) signaling in the promotion of human keratinocyte migration by a collagen matrix and bovine pituitary extract. We found that pharmacological inhibition of the PKCδ pathway completely blocks migration. Using a lentivirus-based vector system, which offers more than 90% gene transduction efficiency to human keratinocytes, we show that the kinase-defective mutant of PKCδ (K376R) dramatically inhibits human keratinocyte migration. Furthermore, PKCδ is activated in migrating human keratinocytes. These observations indicate for the first time that the PKCδ pathway plays an important role in the control of human keratinocyte migration.
ISSN:0014-4827
1090-2422
DOI:10.1006/excr.2001.5422