Epidermal growth factor reduces the development of necrotizing enterocolitis in a neonatal rat model.
Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of prematurely born infants. Maternal milk plays an important protective role against NEC development and is the major source of epidermal growth factor (EGF) for neonates. The aim of this study was to examine the effect of orally administered EGF on the incidence of NEC in a neonatal rat model. Newborn rats were artificially fed either with growth factor-free rat milk substitute (RMS) or RMS supplemented with 500 ng/ml of EGF (RMS+EGF). Experimental NEC was induced by exposure to asphyxia and cold stress. Development of NEC was evaluated by gross and histological scoring of damage in the ileum. Ileal EGF receptor (EGF-R), EGF, and transforming growth factor-alpha mRNA expression was assessed by RT competitive-PCR, and the EGF-R was localized by immunohistochemistry. EGF supplementation of formula reduced the incidence and severity of NEC in rats (13/16 RMS vs. 4/13 RMS+EGF). Ileal EGF-R mRNA expression was markedly increased in the RMS group compared with RMS+EGF. Enhanced EGF-R expression in the RMS group was localized predominantly in the epithelial cells of injured ileum. These data suggest a new potential therapeutic approach for the prevention and treatment of NEC.
Dvorak
Bohuslav
B
Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona 85724, USA. dvorakb@peds.arizona.edu
Halpern
Melissa D
MD
Holubec
Hana
H
Williams
Catherine S
CS
McWilliam
Debra L
DL
Dominguez
Jessica A
JA
Stepankova
Renata
R
Payne
Claire M
CM
McCuskey
Robert S
RS
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control*; D004815:Epidermal Growth Factor / Q000235:genetics / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D007082:Ileum / Q000473:pathology; D015994:Incidence; D008892:Milk; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016211:Transforming Growth Factor alpha / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects
D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors