Wound fluid-derived heparin-binding EGF-like growth factor (HB-EGF) is synergistic with insulin-like growth factor-I for Balb/MK keratinocyte proliferation.
Epidermal cell proliferation is required for re-epithelialization during wound repair. Re-epithelialization of partial thickness excisional wounds in pigs is complete by 6 days after injury. The presence of insulin-like growth factor-I (IGF-I) and heparin-binding molecules that are mitogenic for keratinocytes was examined in wound fluid obtained daily from these wounds. Two significant heparin-binding growth factor activities for Balb/MK keratinocytes were detected, a major one that was eluted from a heparin affinity column with 1.1 M NaCl and a minor one with 0.5 M NaCl. These activities appeared 1 day after injury, were maximal by 2-3 days later, and disappeared by 6 days after injury. The molecule eluting with 1.1 M NaCl was heparin-binding EGF-like (HB-EGF). The levels of IGF-I in wound fluid were 45-90 ng/ml during the first 3 days following injury, decreased thereafter, and were not detectable 6 days after injury. IGF-I at 100 ng/ml, increased HB-EGF mitogenic activity for Balb/MK keratinocytes by 40-50 fold. We conclude that the synergism between IGF-I and HB-EGF and their relative concentration at the various days after injury may be important variables for regulating re-epithelialization during wound repair.
Marikovsky
M
M
Department of Cell Biology, The Weizmann Institute of Science, Rehovot Israel.
Vogt
P
P
Eriksson
E
E
Rubin
J S
JS
Taylor
W G
WG
Joachim
S
S
Klagsbrun
M
M
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000032:analysis* / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D014945:Wound Healing; D014947:Wounds and Injuries / Q000378:metabolism*
C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D006493:Heparin