Cutaneous wound reepithelialization is compromised in mice lacking functional Slug (Snai2)
| Autor: | Allison E. Parent, Kimberly M. Newkirk, Donna F. Kusewitt, Changsun Choi, Heather L. Chandler, Stacey L. Fossey, Laurie G. Hudson |
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| Rok vydání: | 2009 |
| Předmět: |
Keratinocytes
Male Pathology medicine.medical_specialty Slug Dermatology Biochemistry Article Mice In vivo Skin Ulcer Keratin medicine Animals Epithelial–mesenchymal transition Molecular Biology Skin Mice Knockout chemistry.chemical_classification Wound Healing integumentary system biology fungi Cadherins biology.organism_classification Radiation Injuries Experimental chemistry Chronic Disease embryonic structures Keratin 8 Keratins Immunohistochemistry Female Snail Family Transcription Factors Wound healing Ex vivo Transcription Factors |
| Zdroj: | Journal of Dermatological Science. 56:19-26 |
| ISSN: | 0923-1811 |
| Popis: | Background: Keratinocytes at wound margins undergo partial epithelial to mesenchymal transition (EMT). Based on previous in vitro and ex vivo findings, Slug (Snai2), a transcriptional regulator of EMT in development, may play an important role in this process. Objectives: This study was designed to validate an in vivo role for Slug in wound healing. Methods: Excisional wounds in Slug null and wild type mice were examined histologically at 6, 24, 48, and 72 h after wounding; reepithelialization was measured and immunohistochemistry for keratins 8, 10, 14, and 6 and E-cadherin was performed. In 20 Slug null and 20 wild type mice exposed three times weekly to two minimal erythemal doses of UVR, the development of non-healing cutaneous ulcers was documented. Ulcers were examined histologically and by immunohistochemistry. Results: The reepithelialization component of excisional wound healing was reduced 1.7-fold and expression of the Slug target genes keratin 8 and E-cadherin was increased at wound margins in Slug null compared to wild type mice. In contrast, no differences in expression of keratins 10 or 14 or in markers of proliferation K6 and Ki-67 were observed. Forty per cent of Slug null mice but no wild type mice developed non-healing cutaneous ulcers in response to chronic UVR. Keratinocytes at ulcer margins expressed high levels of keratin 8 and retained E-cadherin expression, thus resembling excisional wounds. Conclusion: Slug is an important modulator of successful wound repair in adult tissue and may be critical for maintaining epidermal integrity in response to chronic injury. |
| Databáze: | OpenAIRE |
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