Endogenous production of heparin-binding EGF-like growth factor during murine partial-thickness burn wound healing.
Heparin-binding EGF-like growth factor (HB-EGF), a potent epithelial cell mitogen, has been identified in human burn blister fluid and excised human burn wounds. Topical application of HB-EGF to murine partial-thickness scald burns accelerated reepithelialization, increased keratinocyte proliferation, and enhanced production of endogenous transforming growth factor-alpha in the healing wounds. The goal of the present study was to examine the production of endogenous HB-EGF and transforming growth factor-alpha (TGF-alpha) in a murine partial-thickness scald burn model. Keratinocyte proliferation was assessed by 5-bromo-deoxyuridine incorporation, and tissue sections were examined by in situ hybridization for HB-EGF mRNA expression and by immunohistochemistry for HB-EGF and TGF-alpha production. HB-EGF mRNA expression and production of HB-EGF and TGF-alpha proteins by both marginal surface keratinocytes and hair follicle epithelial cells reached a maximum by postburn day five and decreased thereafter. This corresponded to the peak period of keratinocyte proliferation. We conclude that HB-EGF and TGF-alpha act in conjunction to stimulate wound healing following thermal injury.
Cribbs
Randolph K
RK
Department of Pediatric Surgery, Children's Hospital and The Ohio State University, Columbus, Ohio 43205, USA.
Harding
Paul A
PA
Luquette
Mark H
MH
Besner
Gail E
GE
D000818:Animals; D002056:Burns / Q000378:metabolism* / Q000503:physiopathology; D002455:Cell Division; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000502:physiology*; D006493:Heparin / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000502:physiology*; D014945:Wound Healing
C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D006493:Heparin