Mice lacking beta6 integrin in skin show accelerated wound repair in dexamethasone impaired wound healing model.
Integrin alphavbeta6 is an epithelial-specific receptor that is absent from the healthy epidermis but synthesized de novo during wound repair. However, its function in wound repair is unknown. Integrin-mediated transforming growth factor-beta1 (TGF-beta1) activation is the main activation mechanism of this key cytokine in vivo. Impaired wound healing caused by glucocorticoids is a major clinical problem and is associated with a disturbed balance of TGF-beta1 activity. Therefore, alphavbeta6 integrin-mediated regulation of TGF-beta1 activity may be involved in this process. To determine the function of alphavbeta6 integrin in glucocorticoid-induced impaired wound healing, both beta6 integrin-deficient (beta6-/-) and wild-type mice were exposed to dexamethasone treatment. Multiple wound parameters, keratinocyte proliferation, inflammation, and TGF-beta1 activation were assessed. Wound healing was significantly accelerated in the dexamethasone-treated beta6-/- mice compared with the corresponding wild-type mice. The dexamethasone-treated beta6-/- mice showed enhanced keratinocyte proliferation in both wound epithelium and hair follicles while the production of proinflammatory cytokines and TGF-beta1 activation were reduced. Accelerated wound repair in the dexamethasone-treated beta6-/- mice might be associated with the reduced antiproliferative and proinflammatory effects of TGF-beta1. Inhibition of alphavbeta6 integrin may provide a future target for treatment of impaired wound healing.
Xie
Yanshuang
Y
Department of Oral Biological and Medical Sciences, Faculty of Dentistry, The University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Gao
Kai
K
Häkkinen
Lari
L
Larjava
Hannu S
HS
D000818:Animals; D001706:Biopsy; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005938:Glucocorticoids / Q000627:therapeutic use; D007150:Immunohistochemistry; D039641:Integrin beta Chains / Q000378:metabolism*; D008297:Male; D051379:Mice; D011379:Prognosis; D012867:Skin / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*; D014947:Wounds and Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D005938:Glucocorticoids; D039641:Integrin beta Chains; D053773:Transforming Growth Factor beta1; C072170:integrin beta6; D003907:Dexamethasone