The Effect of a Myostatin Antagonist on the Healing of Burn Wounds in Skin.

Abstract

The body's remarkable ability to repair itself from damage is both very useful and extremely complex. The wound healing system is characterised by four overlapping phases: hemostasis, inflammation, proliferation, and remodelling. It is designed to heal rapidly and efficiently any breach in the protective barrier we call skin, in order to restore normal body function in the quickest possible time. However, pathological conditions such as keloids or hypertrophic scar may arise if events in the wound healing cascade are not coordinated properly, which can lead to loss of skin function and disfigurement. The purpose of this study was to determine whether myostatin plays a role in the healing of burn wounds in skin. Myostatin is best known for its powerful negative regulation of muscle development. Absence of myostatin results in a heavy muscling phenotype, whereas over-expression is associated with muscle wasting conditions. Recently, myostatin has been shown to be involved in muscle wound healing, where knockout of the myostatin gene resulted in improved healing, with decreased fibrotic scar tissue formation. It is noteworthy that the cell surface receptor to which myostatin binds is also present in skin. In consideration of this information the prospect of myostatin involvement in skin biology represents a gap in scientific knowledge. Therefore, the present investigation was designed to ascertain whether the effects of myostatin in muscle regeneration can also be seen in skin wound healing. To this end, a mouse burn wound model was designed to determine the efficacy of antagonising myostatin to bring about improved healing and decreased fibrosis of skin burns. Wounds of mice treated with the myostatin antagonist showed no significant difference compared to saline-treated controls in collagen content at any time point. Gene expression studies on TGF-β1, TGF-β3, decorin and fibromodulin revealed that differences between antagonist-treated and saline-treated groups were possibly masked by the effect of the burn injury but were present in uninjured skin. Similarly, uninjured skin of antagonist-treated animals exhibited a significantly higher fluid content than uninjured skin of saline-treated animals, whereas the effect was not significant in burned skin between treatments. Histological analysis revealed that antagonist-treated wounds showed evidence of decreased wound contraction which may indicate improved scar resolution and decreased risk of fibrosis. Interestingly, the gene expression results in many ways parallel those seen in foetal skin, which after injury, heals without scar. These results warrant further study into the subject area, especially to observe whether further improvements can be made by adjusting the treatment regimen.