Defects in keratinocyte activation during wound healing in the syndecan-1-deficient mouse
Author:
Stepp Mary Ann12, Gibson Heather E.3, Gala Purvi H.1, Iglesia Drina D. Sta.1, Pajoohesh-Ganji Ahdeah1, Pal-Ghosh Sonali1, Brown Marcus1, Aquino Christopher1, Schwartz Arnold M.4, Goldberger Olga3, Hinkes Michael T.3, Bernfield Merton3
Affiliation:
1. Department of Anatomy and Cell Biology, The George Washington University Medical School, Washington DC 20037, USA 2. Department of Ophthalmology, The George Washington University Medical School,Washington DC 20037, USA 3. Division of Developmental and Newborn Biology, Department of Pediatrics,Harvard Medical School, Boston, MA 02115, USA 4. Department of Pathology, The George Washington University Medical School,Washington DC 20037, USA
Abstract
Mice lacking syndecan-1 are viable, fertile and have morphologically normal skin, hair and ocular surface epithelia. While studying the response of these mice to corneal epithelial and skin wounding, we identified defects in epithelial cell proliferation and regulation of integrin expression. mRNA profiling of corneal epithelial tissues obtained from wild-type and syndecan-1-/- mice suggest that these defects result from differences in overall gene transcription. In the cornea,syndecan-1-/- epithelial cells migrate more slowly, show reduced localization of α9 integrin during closure of wounds and fail to increase their proliferation rate 24 hours after wounding. In the skin, we did not document a migration defect after full thickness wounds but did observe cell proliferation delays and reduced localization of α9 integrin in the syndecan-1-/- epidermis after dermabrasion. Despite increased cell proliferation rates in the uninjured syndecan-1-/- epidermis and the corneal epithelium, morphologically normal epithelial thickness is maintained prior to injury; however, wounding is accompanied by prolonged hypoplasia in both tissues. Analyses of integrin protein levels in extracts from full thickness skin, revealed increased levels of α3 and α9 integrins both prior to injury and after hair removal in syndecan-1-/- mice but no increase 2 days after dermabrasion. These data for the first time show involvement of α9 integrin in skin wound healing and demonstrate essential roles for syndecan-1 in mediating cell proliferation and regulation of integrin expression in normal and wounded epithelial tissues.
Publisher
The Company of Biologists
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