α3β1 integrin–controlled Smad7 regulates reepithelialization during wound healing in mice

Abstract

Effective reepithelialization after injury is essential for correct wound healing. The upregulation of keratinocyte α3β1 integrin during reepithelialization suggests that this adhesion molecule is involved in wound healing; however, its precise role in this process is unknown. We have shown here that retarded reepithelialization in Itga3 -/-mouse skin wounds is due predominantly to repressed TGF-β1-mediated responses. Specifically, expression of the inhibitor of TGF-β1-signaling Smad7 was elevated in Itga3 -/-keratinocytes. Indeed, in vivo blockade of Smad7 increased the rate of reepithelialization in Itga3 -/-and WT wounds to similar levels. Our data therefore indicate that the function of α3β1 integrin as a mediator of keratinocyte migration is not essential for reepithelialization but suggest instead that α3β1 integrin has a major new in vivo role as an inhibitor of Smad7 during wound healing. Moreover, our study may identify a previously undocumented function for Smad7 as a regulator of reepithelialization in vivo and implicates Smad7 as a potential novel target for the treatment of cutaneous wounds.

Erythropoietin improves skin wound healing and activates the TGF-β signaling pathway

“…32 Accordingly, in vivo blockade of Smad7 is reported to increase the rate of reepithelialization during wound healing in mice. 33 In our study, EPO did not markedly change Smad7 mRNA expression, but the expression of Smad2, -3, and -4. This results in a dysbalance of Smads in favor of the agonistic Smad proteins.…”

Silver nanoparticles/chitosan oligosaccharide/poly(vinyl alcohol) nanofiber promotes wound healing by activating TGFβ1/Smad signaling pathway

“…43,44 Thus, the inhibition of Smad7 is thought to increase the rate of wound repair. 45 Our results indicated that PVA/COS-AgNPs nanofiber treatment resulted in significantly increased TGFβ1, TGFβRI, TGFβRII, collagen I, collagen III, and fibronectin mRNA expression during the early stage of wound healing. Conversely, SB431542-induced inhibition of the TGFβ1/ Smad signaling pathway downregulated the expression of these genes.…”

Cell-Extracellular Matrix Interactions in Normal and Diseased Skin

“…Wound healing is also compromised when the a3 integrin subunit is deleted in epidermal cells and this is because of a failure to up-regulate Smad7, an inhibitor of TGF-b1 signaling (Reynolds et al 2008).…”