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Abstract

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 (2 mg/mL) in vivo, immediately postburn accelerated healing, promoted faster reepithelialization (3 days: phosphate-buffered saline (PBS), 8.90.3mm diameter vs. MT-I/II, 7.10.7 mm; 7 days: PBS 5.80.98mm vs. MT-I/II, 3.61.0 mm, p < 0.05) and reduced epidermal thickness (MT-I/II: 454 mm vs. PBS: 10119 mm, 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.

Item Type:	Article
Authors/Creators:	Morellini, NM and Giles, NL and Rea, S and Adcroft, AF and Falder, S and King, CE and Dunlop, SA and Beazley, LD and West, AK and Wood, FM and Fear, MW
Journal or Publication Title:	Wound Repair and Regeneration
ISSN:	1067-1927
DOI / ID Number:	https://doi.org/10.1111/j.1524-475X.2008.00418.x
Additional Information:	The definitive published version is available online at: http://interscience.wiley.com
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