Mice lacking beta6 integrin in skin show accelerated wound repair in dexamethasone impaired wound healing model.

Abstract

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.

• Authors: Yanshuang Xie, Kai Gao, Lari Häkkinen, Hannu S Larjava
• Journal: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society (Wound Repair Regen) 2009 May-Jun Vol. 17 Issue 3 Pg. 326-39 ISSN: 1524-475X [Electronic] United States
• PMID: 19660040 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucocorticoids
• Integrin beta Chains
• Transforming Growth Factor beta1
• integrin beta6
• Dexamethasone

Topics

• Animals
• Biopsy
• Cell Proliferation (drug effects)
• Dexamethasone (therapeutic use)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Glucocorticoids (therapeutic use)
• Immunohistochemistry
• Integrin beta Chains (metabolism)
• Male
• Mice
• Prognosis
• Skin (injuries, metabolism, pathology)
• Transforming Growth Factor beta1 (metabolism)
• Wound Healing (drug effects, physiology)
• Wounds and Injuries (drug therapy, metabolism, pathology)