Accelerated closure of skin wounds in mice deficient in the homeobox gene Msx2

Abstract

Differences in cellular competence offer explanation of differences in the healing capacity of tissues of various ages and conditions. The homeobox family of genes plays key roles in governing cellular competence. Of these, we hypothesize that Msx2 is a strong candidate regulator of competence in skin wound healing because it is expressed in the skin during fetal development at stage of scarless healing, affects postnatal digit regeneration, and is re-expressed transiently during postnatal skin wound repair. To address if Msx2 affects cellular competence in injury repair, three millimeter full thickness excisional wounds were created on the back of C.Cg-Msx2tm1Rilm/Mmcd (Msx2 null) mice and the healing pattern was compared with that of the WT mice. Results show that Msx2 null mice exhibited faster wound closure with accelerated re-epithelialization plus earlier appearance of keratin markers for differentiation and increased level of smooth muscle actin and tenascin in the granulation tissue. In vitro, keratinocytes of Msx2 null mice exhibit increased cell migration and the fibroblasts stronger collagen gel contraction. Thus, our results suggest that Msx2 regulates cellular competence of keratinocytes and fibroblasts in skin injury repair.

MicroRNA-21 is an important downstream component of BMP signalling in epidermal keratinocytes

“…Id1-3 are established targets for BMP signalling, and they mediate its effect on cell differentiation (Langlands et al, 2000;Sharov et al, 2003). Msx2 also mediates the effects of BMP signalling during skin development and in postnatal hair follicles, as well as contributing to re-epithelialisation in the epidermis (Yeh et al, 2009). This suggests that the effects of BMP on cell differentiation are likely to occur in an miR-21-independent manner.…”

A Review of the Role of Mechanical Forces in Cutaneous Wound Healing

“…Such regenerative capabilities are lost prior to birth presumably with the signalling pathways responsible for them being rendered dormant. Transcription factors that stimulate organogenesis and homeobox genes are thought to be more active in the fetus and may initiate fetal skin wound repair [115]. Increased understanding of such signalling pathways may allow their reactivatation and much research has focussed on the differences between adult and fetal skin [116][117][118][119][120].…”

Fetal Skin Possesses the Ability to Regenerate Completely: Complete Regeneration of Skin

“…These results suggest that Msx2 regulates the cellular competence of keratinocytes and fibroblasts in skin injury repair. 52 Increased canonical Wnt signaling is observed during postnatal cutaneous wound repair but not during fetal cutaneous wound repair. 53 However, Wnt-4 expression is increased during fetal and postnatal wound repair (Fig.…”