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Publication : αVβ6 integrin promotes corneal wound healing.

First Author  Blanco-Mezquita JT Year  2011
Journal  Invest Ophthalmol Vis Sci Volume  52
Issue  11 Pages  8505-13
PubMed ID  21960555 Mgi Jnum  J:189467
Mgi Id  MGI:5445846 Doi  10.1167/iovs.11-8194
Citation  Blanco-Mezquita JT, et al. (2011) alphaVbeta6 integrin promotes corneal wound healing. Invest Ophthalmol Vis Sci 52(11):8505-13
abstractText  PURPOSE: To appreciate the role of the integrin alphavbeta6 in corneal wound repair, corneal debridement and keratectomy in beta6 knockout (beta6(-/-)) mice were examined. METHODS: Either a 2-mm debridement or keratectomy was made in 129SVE wild type mice (WT) and beta6(-/-) mice and allowed to heal for up to 4 months. The pattern of corneal restoration was studied "in vivo" by slit lamp and in tissue sections by means of both light and electron microscopy. In addition, alphavbeta6, alpha6beta4, laminin, and fibronectin were evaluated by indirect immunofluorescence microscopy and/or Western blot analysis. RESULTS: alphavbeta6 expression was upregulated in migrating corneal epithelium after a keratectomy. Healing rates were unaffected in debridement wounds, but were significantly slowed in keratectomy wounds. Most dramatically, mice lacking alphavbeta6 had a severe defect in basement membrane zone (BMZ) regeneration. Levels of laminin were greatly reduced and no BMZ reformation was observed in transmission electron microscopy (TEM). In addition, hemidesmosome reformation was also impaired in the beta6(-/-) mice. Analysis of the hemidesmosome component alpha6beta4 indicated that normal amounts of this integrin were synthesized, suggesting that the defect was in reassembly of the hemidesmosomes. Finally, fibronectin persisted in the BMZ for as long as 4 months after keratectomy in the beta6(-/-) mice. CONCLUSIONS: It is hypothesized that the lack of alphavbeta6 leads to reduced laminin production during wound repair. This lack of laminin prevents reassembly of the BMZ and mature hemidesmosomes after keratectomy in beta6(-/-) mice.
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