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Expression of Integrin vβ6 and TGF-β in Scarless vs Scar-forming Wound Healing

Ameneh Eslami, Corrie L. Gallant-Behm, David A. Hart, Colin Wiebe, Dariush Honardoust, Humphrey Gardner, Lari Häkkinen and Hannu S. Larjava

Laboratory of Periodontal Biology, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada (AE,CW,DH,LH,HSL); Department of Surgery, Northwestern University, Chicago, Illinois (CLG-B); Department of Surgery, McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada (DAH); and Novartis Institutes for Biomedical Research, Cambridge, Massachusetts (HG)

Correspondence to: Dr. Hannu Larjava, University of British Columbia, Faculty of Dentistry, Department of Oral Biological and Medical Sciences, Laboratory of Periodontal Biology, 2199 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3. E-mail: larjava{at}interchange.ubc.ca

Oral mucosal wounds heal with reduced scar formation compared with skin. The epithelial integrin vβ6 is induced during wound healing, and it can activate fibrogenic transforming growth factor β1 (TGF-β1) and anti-fibrogenic TGF-β3 that play key roles in scar formation. In this study, expression of β6 integrin and members of the TGF-β pathway were studied in experimental wounds of human gingiva and both gingiva and skin of red Duroc pigs using real-time PCR, gene microarrays, and immunostaining. Similar to human wounds, the expression of β6 integrin was induced in the pig wounds 7 days after wounding and remained upregulated >49 days. The vβ6 integrin was colocalized with both TGF-β isoforms in the wound epithelium. Significantly higher expression levels of β6 integrin and TGF-β1 were observed in the pig gingival wounds compared with skin. Early gingival wounds also expressed higher levels of TGF-β3 compared with skin. The spatio-temporal colocalization of vβ6 integrin with TGF-β1 and TGF-β3 in the wound epithelium suggests that vβ6 integrin may activate both isoforms during wound healing. Prolonged expression of vβ6 integrin along with TGF-β3 in the gingival wound epithelium may be important in protection of gingiva from scar formation. (J Histochem Cytochem 57:543–557, 2009)

Key Words: scarless wound healing • transforming growth factor β • vβ6 integrin

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