Appearance of heparin-binding EGF-like growth factor in wound fluid as a response to injury.
Wound fluid was obtained from porcine partial-thickness excisional wounds and analyzed for heparin-binding growth factors. Two heparin-binding growth factor activities were detected, a relatively minor one that was eluted from a heparin affinity column with 0.65 M NaCl and a major one that was eluted with 1.1 M NaCl. These activities were not present in wound fluid 1 hr after injury but appeared 1 day after injury, were maximal 2-3 days after injury, and were not detectable by 8 days after injury. The heparin-binding growth factor eluted with 0.65 M NaCl was identified as a platelet-derived growth factor (PDGF)-like activity by the use of specific anti-PDGF neutralizing antibodies. The heparin-binding growth factor eluted with 1.1 M NaCl was shown to be structurally related to heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) by several criteria, including binding to heparin affinity columns and elution with 1.1 M NaCl, competition with the binding of 125I-EGF to the EGF receptor, triggering phosphorylation of the EGF receptor, immunodetection on a Western blot, and stimulation of fibroblast and keratinocyte growth. It was concluded that HB-EGF is a major growth factor component of wound fluid and, since it is mitogenic for fibroblasts and keratinocytes, that it might play an important role in wound healing.
Marikovsky
M
M
Department of Surgical Research, Children's Hospital, Boston, MA 02115.
Breuing
K
K
Liu
P Y
PY
Eriksson
E
E
Higashiyama
S
S
Farber
P
P
Abraham
J
J
Klagsbrun
M
M
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002196:Capillaries; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D004261:DNA Replication / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D006133:Growth Substances / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D010766:Phosphorylation; D013552:Swine; D014407:Tumor Cells, Cultured; D014947:Wounds and Injuries / Q000503:physiopathology*
D006133:Growth Substances; D010455:Peptides; D004815:Epidermal Growth Factor; D006493:Heparin; D066246:ErbB Receptors