title: Brief treatment with heparin-binding EGF-like growth factor, but not with EGF, is sufficient to accelerate epithelial wound healing.
abstract: BACKGROUND
  Heparin-binding EGF-like growth factor (HB-EGF) contains, in contrast to EGF, a domain that binds to negatively charged glycans on cell surfaces and in extracellular matrix. We speculated that a short exposure to HB-EGF induces prolonged biological effects such as healing of wounds after immobilization in tissues.
  
  
  METHODS
  Epithelial cell sheets in tissue and corneas in organ culture were treated briefly with HB-EGF or EGF and binding of the growth factors, time course of activation of the EGF receptor, and healing of wounds were compared.
  
  
  RESULTS
  Treating human corneal epithelial cells for 2 min with HB-EGF resulted in 8h of detectable activation of the EGF receptor, but activation was much shorter after EGF treatment. A brief treatment with HB-EGF, but not with EGF, induced significant acceleration of healing in wounds in epithelial sheets in tissue and organ culture. Bound HB-EGF was detectable up to 16 h after brief treatments. Neutralizing antibodies added after HB-EGF treatment blocked acceleration of healing, demonstrating the role of bound HB-EGF in accelerating healing.
  
  
  CONCLUSIONS
  A brief exposure to HB-EGF, but not to EGF, is sufficient to induce prolonged activation of the EGF receptor and to enhance healing.
  
  
  CONCLUSIONS
  Bound HB-EGF can serve as a pool that induces prolonged activation of the EGF receptor. EGF has been used experimentally to treat poorly healing wounds, but the frequent applications that are necessary have hampered its use clinically. The findings imply that HB-EGF may be a useful long-acting alternative to EGF.
authors.affiliation: Ophthalmology and Visual Sciences Research Center, the Eye and Ear Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Tolino
authors.forename: Ethan R
authors.initials: ER
authors.lastname: Block
authors.forename: Jes K
authors.initials: JK
authors.lastname: Klarlund
mesh_terms: D000818:Animals; D065306:Corneal Injuries; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011817:Rabbits; D014945:Wound Healing / Q000187:drug effects*
chemical_list: C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors