Exogenous metallothionein-IIA promotes accelerated healing after a burn wound.

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 (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 microg/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 microm vs. PBS: 101+/-19 microm, 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.

• Authors: Natalie M Morellini, Natalie L Giles, Suzanne Rea, Katharine F Adcroft, Sian Falder, Carolyn E King, Sarah A Dunlop, Lyn D Beazley, Adrian K West, Fiona M Wood, Mark W Fear
• Journal: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society (Wound Repair Regen) 2008 Sep-Oct Vol. 16 Issue 5 Pg. 682-90 ISSN: 1524-475X [Electronic] United States
• PMID: 19128263 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Metallothionein

Topics

• Animals
• Burns (drug therapy)
• Cells, Cultured
• Humans
• Metallothionein (therapeutic use)
• Mice
• Mice, Inbred C57BL
• Time Factors
• Wound Healing (drug effects)