title: 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.affiliation: School of Animal Biology, University of Western Australia, Crawley, WA 6009, Australia. moreln01@student.uwa.edu.au
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Morellini
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Giles
authors.forename: Suzanne
authors.initials: S
authors.lastname: Rea
authors.forename: Katharine F
authors.initials: KF
authors.lastname: Adcroft
authors.forename: Sian
authors.initials: S
authors.lastname: Falder
authors.forename: Carolyn E
authors.initials: CE
authors.lastname: King
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Dunlop
authors.forename: Lyn D
authors.initials: LD
authors.lastname: Beazley
authors.forename: Adrian K
authors.initials: AK
authors.lastname: West
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Wood
authors.forename: Mark W
authors.initials: MW
authors.lastname: Fear
mesh_terms: D000818:Animals; D002056:Burns / Q000188:drug therapy*; D002478:Cells, Cultured; D006801:Humans; D008668:Metallothionein / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D008668:Metallothionein