TY - JOUR
T1 - Cutaneous wound reepithelialization is compromised in mice lacking functional Slug (Snai2)
AU - Hudson, Laurie G.
AU - Newkirk, Kimberly M.
AU - Chandler, Heather L.
AU - Choi, Changsun
AU - Fossey, Stacey L.
AU - Parent, Allison E.
AU - Kusewitt, Donna F.
N1 - Funding Information:
This work was supported by NIH grants R01 AR42989, R01 GM07381, and P30 CA16672. We thank the histology laboratories at the Ohio State University College of Veterinary Medicine and the Science Park Research Division of the University of Texas M.D. Anderson Cancer Center for their outstanding histology support.
PY - 2009/10
Y1 - 2009/10
N2 - 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.
AB - 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.
KW - Cell adhesion
KW - Keratins
KW - Snail family transcription factors
KW - Wound healing
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U2 - 10.1016/j.jdermsci.2009.06.009
DO - 10.1016/j.jdermsci.2009.06.009
M3 - Article
C2 - 19643582
AN - SCOPUS:69049106307
SN - 0923-1811
VL - 56
SP - 19
EP - 26
JO - Journal of Dermatological Science
JF - Journal of Dermatological Science
IS - 1
ER -