title: Deletion of the heparin-binding epidermal growth factor-like growth factor gene increases susceptibility to necrotizing enterocolitis.
abstract: BACKGROUND
  Necrotizing enterocolitis (NEC) is the leading surgical cause of death in premature infants. We have accumulated evidence supporting a role for heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) in protection of the intestines from NEC. The aim of the current study was to evaluate the effect of loss-of-function of endogenous HB-EGF on susceptibility to NEC.
  
  
  METHODS
  Neonatal HB-EGF((-/-)) knockout (KO) mice and their HB-EGF((+/+)) wild-type (WT) counterparts were exposed to experimental NEC. An additional group of HB-EGF KO pups were also exposed to NEC but had HB-EGF added to their formula. To examine gut barrier function, HB-EGF KO and WT pups received intragastric fluorescein isothiocyanate-labeled dextran (FITC dextran) under basal and stressed conditions, and serum FITC dextran levels were measured.
  
  
  RESULTS
  The WT mice had an incidence of NEC of 53%, whereas HB-EGF KO mice had a significantly increased incidence of NEC of 80% (P = .04). Importantly, administration of exogenous HB-EGF to HB-EGF KO pups significantly reduced the incidence of NEC to 45% (P = .04). Heparin-binding EGF KO mice had significantly increased intestinal permeability compared to WT mice under basal and stressed conditions.
  
  
  CONCLUSIONS
  Our results provide evidence that loss of the HB-EGF gene increases susceptibility to NEC and that administration of exogenous HB-EGF reverses this susceptibility.
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Radulescu
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Yu
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Orvets
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Zhang
authors.forename: Gail E
authors.initials: GE
authors.lastname: Besner
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020345:Enterocolitis, Necrotizing / Q000235:genetics* / Q000517:prevention & control; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010539:Permeability
chemical_list: C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins
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