Abstract
The upregulation of TGF-beta1 and integrin expression during wound healing has implicated these molecules in this process, but their precise regulation and roles remain unclear. Here we report that, notably, mice lacking beta(3)-integrins show enhanced wound healing with re-epithelialization complete several days earlier than in wild-type mice. We show that this effect is the result of an increase in TGF-beta1 and enhanced dermal fibroblast infiltration into wounds of beta(3)-null mice. Specifically, beta(3)-integrin deficiency is associated with elevated TGF-beta receptor I and receptor II expression, reduced Smad3 levels, sustained Smad2 and Smad4 nuclear localization and enhanced TGF-beta1-mediated dermal fibroblast migration. These data indicate that alpha(v)beta(3)-integrin can suppress TGF-beta1-mediated signaling, thereby controlling the rate of wound healing, and highlight a new mechanism for TGF-beta1 regulation by beta(3)-integrins.
MeSH terms
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Animals
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Epithelium / anatomy & histology
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Epithelium / pathology
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Epithelium / physiology*
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Fibroblasts / cytology
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Fibroblasts / metabolism
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HSC70 Heat-Shock Proteins
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HSP70 Heat-Shock Proteins / genetics
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HSP70 Heat-Shock Proteins / metabolism
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In Situ Hybridization
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Integrin beta3 / genetics
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Integrin beta3 / metabolism*
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Mice
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Mice, Knockout
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Receptors, Transforming Growth Factor beta / genetics
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Receptors, Transforming Growth Factor beta / metabolism
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Signal Transduction / physiology*
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Smad Proteins
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism*
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Transforming Growth Factor beta1
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Wound Healing / physiology*
Substances
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DNA-Binding Proteins
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HSC70 Heat-Shock Proteins
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HSP70 Heat-Shock Proteins
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Hspa8 protein, mouse
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Integrin beta3
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Receptors, Transforming Growth Factor beta
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Smad Proteins
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Tgfb1 protein, mouse
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Trans-Activators
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Transforming Growth Factor beta
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Transforming Growth Factor beta1