026 Altered Skin Wound Healing in Homeobox Gene Msx-2 Knockout Mice

Abstract

Homeobox genes are transcription factor that form nested patterns in specific regions throughout the body. Homeobox genes are important for wound healing study because some have been shown to be related to scarless fetal wound healing. Muscle segment homeobox-2 (Msx-2) is a homeobox gene commonly expressed at sites of epithelial-mesenchymal interactions during tissue morphogenesis. Overexpression of Msx-2 leads to craniosynostosis, epidermal dysplasia, and abnormal hair growth. A knockout of this gene causes pleiotropic defects in bone growth, cyclic alopecia, and a thinner dermis. While Msx-2 has been found to play many critical roles in development, no functional study has been conducted on Msx-2 and wound healing. We hypothesize that Msx-2 regulates skin morphogenesis during wound repair which was tested by studying excisional skin wound closure. Isolated keratinocytes and dermal fibroblasts of Msx-2 WT and KO mice were also studied to determine the effects of Msx-2. Results showed that Msx-2 mRNA was induced in epidermis and dermis during wound repair. Additionally, Msx-2 KO mice exhibited enhanced re-epithelialization and faster wound closure than the WT control. These repair phenotypes may be attributed to keratinocyte motility and fibroblast interaction with collagen matrix as, in vitro, Msx-2 KO keratinocytes exhibited increased motility, and fibroblasts show stronger collagen matrix contraction and expressed higher levels of α2β1 than WT control. Msx-2 KO fibroblasts were refractory to BMP4 in collagen matrix contraction, demonstrating a disruption in the Msx-2 pathway. In conclusion, Msx-2 may regulate skin morphogenesis during repair at both epithelial and mesenchymal levels. This work was supported by NIH grant R01GM055081(TLT).