Loss of the Desmosomal Component Perp Impairs Wound Healing In Vivo

Epithelial wound closure is a complex biological process that relies on the concerted action of activated keratinocytes and dermal fibroblasts to resurface and close the exposed wound. Modulation of cell-cell adhesion junctions is thought to facilitate cellular proliferation and migration of keratin...

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Bibliographic Details
Published in:Dermatology Research and Practice 2010-01, Vol.2010 (1), p.308-318
Main Authors: Beaudry, Veronica G., Ihrie, Rebecca A., Jacobs, Suzanne B. R., Nguyen, Bichchau, Pathak, Navneeta, Park, Eunice, Attardi, Laura D.
Format: Article
Language:English
Subjects:
Cancer
Cell adhesion & migration
Cell migration
Immunoglobulins
Keratin
Keratinocytes
Physiological aspects
Rodents
Studies
Wound healing
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Summary:Epithelial wound closure is a complex biological process that relies on the concerted action of activated keratinocytes and dermal fibroblasts to resurface and close the exposed wound. Modulation of cell-cell adhesion junctions is thought to facilitate cellular proliferation and migration of keratinocytes across the wound. In particular, desmosomes, adhesion complexes critical for maintaining epithelial integrity, are downregulated at the wound edge. It is unclear, however, how compromised desmosomal adhesion would affect wound reepithelialization, given the need for a delicate balance between downmodulating adhesive strength to permit changes in cellular morphology and maintaining adhesion to allow coordinated migration of keratinocyte sheets. Here, we explore the contribution of desmosomal adhesion to wound healing using mice deficient for the desmosomal component Perp. We find that Perp conditional knockout mice display delayed wound healing relative to controls. Furthermore, we determine that while loss of Perp compromises cell-cell adhesion, it does not impair keratinocyte proliferation and actually enhances keratinocyte migration in in vitro assays. Thus, Perp's role in promoting cell adhesion is essential for wound closure. Together, these studies suggest a role for desmosomal adhesion in efficient wound healing.
ISSN:1687-6105
1687-6113
DOI:10.1155/2010/759731