Epidermal growth factor reduces intestinal apoptosis in an experimental model of necrotizing enterocolitis

Jessica A. Clark, Robert H. Lane, Nicole K. MacLennan, Hana Holubec, Katerina Dvorakova, Melissa D Halpern, Catherine S. Williams, Claire M. Payne, Bohuslav Dvorak

Research output: Contribution to journalArticle

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Abstract

Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Although end-stage NEC is characterized histopathologically as extensive necrosis, apoptosis may account for the initial loss of epithelium before full development of disease. We have previously shown that epidermal growth factor (EGF) reduces the incidence of NEC in a rat model. Although EGF has been shown to protect intestinal enterocytes from apoptosis, the mechanism of EGF-mediated protection against NEC is not known. The aim of this study was to investigate if EGF treatment elicits changes in expression of apoptotic markers in the ileum during the development of NEC. With the use of a well-established neonatal rat model of NEC, rats were divided into the following three experimental groups: dam fed (DF), milk formula fed (NEC), or fed with formula supplemented with 500 ng/ml EGF (NEC+EGF). Changes in ileal morphology, gene and protein expression, and histological localization of apoptotic regulators were evaluated. Anti-apoptotic Bcl-2 raRNA levels were markedly reduced and pro-apoptotic Bax mRNA levels were markedly elevated in the NEC group compared with DF controls. Supplementation of EGF into formula significantly increased anti-apoptotic Bcl-2 mRNA, whereas pro-apoptotic Bax was significantly decreased. The Bax-to-Bcl-2 ratio for mRNA and protein was markedly decreased in NEC+EGF animals compared with the NEC group. The presence of caspase-3-positive epithelial cells was markedly reduced in EGF-treated rats. These data suggest that alteration of the balance between pro-and anti-apoptotic proteins in the site of injury is a possible mechanism by which EGF maintains intestinal integrity and protects intestinal epithelium against NEC injury.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume288
Issue number4 51-4
DOIs
StatePublished - Apr 2005

Fingerprint

Necrotizing Enterocolitis
Epidermal Growth Factor
Theoretical Models
Apoptosis
Apoptosis Regulatory Proteins
Messenger RNA
Intestinal Diseases
Enterocytes
Wounds and Injuries
Intestinal Mucosa
Ileum
Premature Infants
Caspase 3
Milk
Proteins
Necrosis
Epithelium
Epithelial Cells

Keywords

  • Bax
  • Bcl-2
  • Epithelial injury
  • Ileum
  • Rat

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Epidermal growth factor reduces intestinal apoptosis in an experimental model of necrotizing enterocolitis. / Clark, Jessica A.; Lane, Robert H.; MacLennan, Nicole K.; Holubec, Hana; Dvorakova, Katerina; Halpern, Melissa D; Williams, Catherine S.; Payne, Claire M.; Dvorak, Bohuslav.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 288, No. 4 51-4, 04.2005.

Research output: Contribution to journalArticle

Clark, Jessica A. ; Lane, Robert H. ; MacLennan, Nicole K. ; Holubec, Hana ; Dvorakova, Katerina ; Halpern, Melissa D ; Williams, Catherine S. ; Payne, Claire M. ; Dvorak, Bohuslav. / Epidermal growth factor reduces intestinal apoptosis in an experimental model of necrotizing enterocolitis. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2005 ; Vol. 288, No. 4 51-4.
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