Exogenous metallothionein-IIA promotes accelerated healing after a burn wound
Morellini, NM and Giles, NL and Rea, S and Adcroft, KF and Falder, S and King, CE and Dunlop, SA and Beazley, LD and West, AK and Wood, FM and Fear, MW, Exogenous metallothionein-IIA promotes accelerated healing after a burn wound, Wound Repair and Regeneration, 16, (5) pp. 682-690. ISSN 1067-1927 (2008) [Refereed Article]
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 (Zn7-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 Zn7-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 Zn7-MT-IIA (2áμg/mL) in vivo, immediately postburn accelerated healing, promoted faster reepithelialization (3 days: phosphate-buffered saline (PBS), 8.9▒0.3ámm diameter vs. MT-I/II, 7.1▒0.7ámm; 7 days: PBS 5.8▒0.98ámm vs. MT-I/II, 3.6▒1.0ámm, p<0.05) and reduced epidermal thickness (MT-I/II: 45▒4áμm vs. PBS: 101▒19áμm, p<0.05) compared with controls. Our data suggest that exogenous Zn7-MT-IIA may prove a valuable therapeutic for patients with burns and other skin injuries.