Severe injury to the epidermal barrier often results in scarring and life-long functional deficits, the outcome worsening with a number of factors including time taken to heal. We have investigated the potential of exogenous metallothionein IIA (Zn-7-MT-IIA), a naturally occurring small cysteine-rich protein, to accelerate healing of burn wounds in a mouse model. Endogenous MT-I/II expression increased in basal keratinocytes concurrent with reepithelialization after a burn injury, indicating a role for MT-I/II in wound healing. In vitro assays of a human keratinocyte cell line indicated that, compared with saline controls, exogenous Zn-7-MT-IIA significantly increased cell viability by up to 30% (p < 0.05), decreased apoptosis by 13% (p < 0.05) and promoted keratinocyte migration by up to 14% (p < 0.05), all properties that may be desirable to promote rapid wound repair. Further in vitro assays using immortalized and primary fibroblasts indicated that Zn7-MT-IIA did not affect fibroblast motility or contraction (p > 0.05). Topical administration of exogenous Zn-7-MT-IIA (2 mu g/mL) in vivo, immediately postburn accelerated healing, promoted faster reepithelialization (3 days: phosphate-buffered saline (PBS), 8.9 +/- 0.3 mm diameter vs. MT-I/II, 7.1 +/- 0.7 mm; 7 days: PBS 5.8 +/- 0.98 mm vs. MT-I/II, 3.6 +/- 1.0 mm, p < 0.05) and reduced epidermal thickness (MT-I/II: 45 +/- 4 mu m vs. PBS: 101 +/- 19 mu m, p < 0.05) compared with controls. Our data suggest that exogenous Zn-7-MT-IIA may prove a valuable therapeutic for patients with burns and other skin injuries.
Morellini, N. M., Giles, N. L., Rea, S., Adcroft, K. F., Falder, S., King, C. E., ... West, A. (2008). Exogenous metallothionein-IIA promotes accelerated healing after a burn wound. Wound Repair and Regeneration, 16, 682-690. https://doi.org/10.1111/j.1524-475X.2008.00418.x