Transforming Growth Factor Beta 3 Is Required for Excisional Wound Repair In Vivo

Abstract

Wound healing is a complex process that relies on proper levels of cytokines and growth factors to successfully repair the tissue. Of particular interest are the members of the transforming growth factor family. There are three TGF-ß isoforms–TGF- ß 1, 2, and 3, each isoform showing a unique expression pattern, suggesting that they each play a distinct function during development and repair. Previous studies reported an exclusive role for TGF-ß 3 in orofacial development and a potent anti-scarring effect. However, the role of TGF- ß 3 in excisional wound healing and keratinocyte migration remains poorly understood. We tested the effect of TGF-ß 3 levels on excisional cutaneous wounds in the adult mouse by directly injecting recombinant TGF-ß 3 or neutralizing antibody against TGF-ß 3 (NAB) in the wounds. Our results demonstrate that TGF-ß 3 does not promote epithelialization. However, TGF-ß 3 is necessary for wound closure as wounds injected with neutralizing antibody against TGF-ß 3 showed increased epidermal volume and proliferation in conjunction with a delay in keratinocyte migration. Wild type keratinocytes treated with NAB and Tgfb3-deficient keratinocytes closed an in vitro scratch wound with no delay, suggesting that our in vivo observations likely result from a paracrine effect.

Interferon regulatory factor 6 regulates keratinocyte migration

“…Irf6 is present at the wound edge and in the neoformed epidermis following excisional wounding We used our excisional murine wound-healing model (Le et al, 2012) to evaluate the expression of Irf6 in adult mice. We observed the presence of Irf6 in keratinocytes of unwounded adult mice (Fig.…”

“…Two 6-mm punch biopsies were performed on the back of 8-12-week-old wild-type animals, as described previously (Le et al, 2012). Animals (n54-6 per group) were euthanized at 1, 4, 7 and 11 days post-wounding, and wounds were fixed in 4% paraformaldehyde.…”

“…Animals (n54-6 per group) were euthanized at 1, 4, 7 and 11 days post-wounding, and wounds were fixed in 4% paraformaldehyde. Serial sections and immunostaining were performed as described previously Le et al, 2012).…”

Growth factor pathways in hypertrophic scars: Molecular pathogenesis and therapeutic implications

“…Moreover, treatment with TGF-b3 resulted in less ECM synthesis and fibroblast differentiation compared with treatment with TGF-b1 and b2 in human vocal fold fibroblasts, supporting that the TGF-b isoforms might have distinct roles in hypertrophic scars [32]. Additionally, TGF-b3 was found to be necessary for wound closure because wounds injected with TGFb3 neutralizing antibody exhibited increased epidermal volume and proliferation in conjunction with a delay in keratinocyte migration [33].…”

The Role of Growth Factor Sadat-Habdan Mesenchymal Stimulating Peptide in Healing of Burn Wounds

“…Transforming growth factor A1 isolated from blood platelets has a major effect on tissues of mesenchymal origin, hence in wound healing. 7,8 Recently, erythropoietin was shown to improve angiogenesis and wound healing in experimental burn wounds. 9 Leptin is a potent direct and angiogenic factor that stimulates endothelial cell migration and activation in vitro and angiogenesis in vivo.…”