title: Defects in keratinocyte activation during wound healing in the syndecan-1-deficient mouse.
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 alpha9 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 alpha9 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 alpha3 and alpha9 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 alpha9 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.
authors.affiliation: Department of Anatomy and Cell Biology, The George Washington University Medical School, Washington DC 20037, USA. mastepp@gwu.edu
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Stepp
authors.forename: Heather E
authors.initials: HE
authors.lastname: Gibson
authors.forename: Purvi H
authors.initials: PH
authors.lastname: Gala
authors.forename: Drina D Sta
authors.initials: DD
authors.lastname: Iglesia
authors.forename: Ahdeah
authors.initials: A
authors.lastname: Pajoohesh-Ganji
authors.forename: Sonali
authors.initials: S
authors.lastname: Pal-Ghosh
authors.forename: Marcus
authors.initials: M
authors.lastname: Brown
authors.forename: Christopher
authors.initials: C
authors.lastname: Aquino
authors.forename: Arnold M
authors.initials: AM
authors.lastname: Schwartz
authors.forename: Olga
authors.initials: O
authors.lastname: Goldberger
authors.forename: Michael T
authors.initials: MT
authors.lastname: Hinkes
authors.forename: Merton
authors.initials: M
authors.lastname: Bernfield
mesh_terms: D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D065306:Corneal Injuries; D039001:Integrin alpha Chains / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011509:Proteoglycans / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012098:Reproduction; D012867:Skin / Q000166:cytology / Q000473:pathology; D053668:Syndecan-1; D053667:Syndecans; D014945:Wound Healing
chemical_list: D039001:Integrin alpha Chains; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; C084613:integrin alpha9