title: Heparin-binding EGF-like growth factor (HB-EGF) protects the intestines from radiation therapy-induced intestinal injury.
abstract: OBJECTIVE
  Radiation therapy (RT) often induces enteritis by inhibiting proliferation and inducing apoptosis. Heparin-binding EGF-like growth factor (HB-EGF) has been shown to protect the intestine in several animal injury models. The objective of this study was to examine whether HB-EGF affects RT-induced intestinal injury.
  
  
  METHODS
  HB-EGF or PBS was administered intraperitoneally to mice daily for 3 days, followed by total body irradiation (TBI). Three days after TBI, intestinal segments were harvested, and BrdU immunohistochemistry was performed to identify proliferating crypts (n=25). Four days after TBI, intestinal segments were harvested and assessed for histologic injury (n=34), and FITC-dextran was administered via gavage with serum FITC-dextran levels quantified to determine gut barrier function (n=18).
  
  
  RESULTS
  Compared to non-HB-EGF-treated irradiated mice, administration of HB-EGF to irradiated mice led to a significantly increased percentage of proliferative crypts (72.6% vs. 50.5%, p=0.001), a significantly decreased percent of histologic sections with severe histologic injury (13.7% vs. 20.3%, p=0.005), and significantly reduced intestinal permeability (18.8 μg/mL vs. 22.6 μg/mL, p=0.02).
  
  
  CONCLUSIONS
  These results suggest that administration of HB-EGF protects the intestines from injury after exposure to radiation therapy. Administration of HB-EGF may represent a novel therapy for the prevention of radiation enteritis in the future.
authors.affiliation: The Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, The Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH 43205, USA.
authors.forename: Mika A B
authors.initials: MA
authors.lastname: Matthews
authors.forename: Daniel
authors.initials: D
authors.lastname: Watkins
authors.forename: Amanda
authors.initials: A
authors.lastname: Darbyshire
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
authors.forename: Gail E
authors.initials: GE
authors.lastname: Besner
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D066257:Heparin-binding EGF-like Growth Factor; D007274:Injections, Intraperitoneal; D036341:Intercellular Signaling Peptides and Proteins / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000293:injuries / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011837:Radiation-Protective Agents
keywords: HB-EGF; Intestines; Permeability; Proliferation; Radiation injury