Cutaneous wound reepithelialization is compromised in mice lacking functional Slug (Snai2).
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.


OBJECTIVE
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 72h 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.


CONCLUSIONS
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.
Hudson
Laurie G
LG
Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, United States.
Newkirk
Kimberly M
KM
Chandler
Heather L
HL
Choi
Changsun
C
Fossey
Stacey L
SL
Parent
Allison E
AE
Kusewitt
Donna F
DF
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002908:Chronic Disease; D005260:Female; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology*; D007633:Keratins / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011833:Radiation Injuries, Experimental / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012883:Skin Ulcer / Q000378:metabolism / Q000473:pathology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics*
D015820:Cadherins; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D007633:Keratins