Augmentation of wound healing with translation initiation factor eIF4E mRNA.
BACKGROUND
Initiation of translation is the rate-limiting step in protein synthesis; eIF4E increases translational efficiency by facilitating ribosome scanning. eIF4E is present in cells in rate-limiting amounts; chronic overexpression of eIF4E causes cell transformation by upregulating growth-related proteins. Biolistic delivery of epidermal growth factor (EGF) increases wound healing; transiently increasing wound eIF4E levels with biolistic mRNA transmission may further augment wound healing without oncogenesis.


METHODS
Midline fascial wounds were created in rats and biolistically treated with gold particles carrying mRNA encoding for hEGF with or without eIF4E prior to suture closure; control animals received blank bullets. The animals were sacrificed at 7 or 14 days for determination of peak wound bursting strength on a tensiometer. Results are expressed as means +/- standard deviation; statistics were via analysis of variance.


RESULTS
[Table: see text].


CONCLUSIONS
Simultaneous biolistic delivery of EGF mRNA with eIF4E mRNA significantly increases wound breaking strength compared to that in control animals or treatment with EGF mRNA alone without risk of cellular transformation. Further studies of translational activation to augment wound healing are warranted.
Schwarz
Karl W
KW
Department of Surgery and the Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Murray
Mary T
MT
Sylora
Roxanne
R
Sohn
Richard L
RL
Dulchavsky
Scott A
SA
D000818:Animals; D019470:Biolistics; D003094:Collagen / Q000032:analysis; D004815:Epidermal Growth Factor / Q000235:genetics; D039561:Eukaryotic Initiation Factor-4E; D005205:Fascia / Q000293:injuries; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010448:Peptide Initiation Factors / Q000235:genetics*; D012333:RNA, Messenger / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013718:Tensile Strength; D016896:Treatment Outcome; D014945:Wound Healing
D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D003094:Collagen