title: E2F-1 is essential for normal epidermal wound repair.
abstract: E2F factors are involved in proliferation and apoptosis. To understand the role of E2F-1 in the epidermis, we screened wild type and E2F-1(-/-) keratinocyte mRNA for genes differentially expressed in the two cell populations. We demonstrate the reduced expression of integrins alpha(5), alpha(6), beta(1), and beta(4) in E2F-1(-/-) keratinocytes associated with reduced activation of Jun terminal kinase and Erk upon integrin stimulation. As a consequence of altered integrin expression and function, E2F-1(-/-) keratinocytes also show impaired migration, adhesion to extracellular matrix proteins, and a blunted chemotactic response to transforming growth factor-gamma1. E2F-1(-/-) keratinocytes, but not dermal fibroblasts, exhibit altered patterns of proliferation, including significant delays in transit through both G(1) and S phases of the cell cycle. Recognizing that proliferation and migration are key for proper wound healing in vivo, we postulated that E2F-1(-/-) mice may exhibit abnormal epidermal repair upon injury. Consistent with our hypothesis, E2F-1(-/-) mice exhibited impaired cutaneous wound healing. This defect is associated with substantially reduced local inflammatory responses and rates of re-epithelialization. Thus, we demonstrate that E2F-1 is indispensable for a hitherto unidentified cell type-specific and unique role in keratinocyte proliferation, adhesion, and migration as well as in proper wound repair and epidermal regeneration in vivo.
authors.affiliation: Department of Pharmacology, Child Health Research Institute, University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Sudhir Jude Anthony
authors.initials: SJ
authors.lastname: D'Souza
authors.forename: Alisa
authors.initials: A
authors.lastname: Vespa
authors.forename: Suranjana
authors.initials: S
authors.lastname: Murkherjee
authors.forename: Amy
authors.initials: A
authors.lastname: Maher
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pajak
authors.forename: Lina
authors.initials: L
authors.lastname: Dagnino
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D018797:Cell Cycle Proteins; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology*; D016193:G1 Phase; D017403:In Situ Hybridization; D016023:Integrins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology*; D014945:Wound Healing
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D016023:Integrins; D014157:Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases