HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/G755    most recent 00172.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (20) Citing Articles via Google Scholar Google Scholar Articles by Clark, J. A. Articles by Dvorak, B. Search for Related Content PubMed PubMed Citation Articles by Clark, J. A. Articles by Dvorak, B.

INFLAMMATION/IMMUNITY/MEDIATORS

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

¹Departments of Pediatrics and Steele Memorial Children's Research Center and ³Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona; and ²Department of Pediatrics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California

Submitted 19 April 2004 ; accepted in final form 3 November 2004

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 mRNA 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.

epithelial injury; ileum; rat; Bcl-2; Bax

This article has been cited by other articles:

				S. Cetin, C. L. Leaphart, J. Li, I. Ischenko, M. Hayman, J. Upperman, R. Zamora, S. Watkins, H. R. Ford, J. Wang, et al. Nitric oxide inhibits enterocyte migration through activation of RhoA-GTPase in a SHP-2-dependent manner Am J Physiol Gastrointest Liver Physiol, May 1, 2007; 292(5): G1347 - G1358. [Abstract] [Full Text] [PDF]

				P. T. Sangild Gut Responses to Enteral Nutrition in Preterm Infants and Animals Experimental Biology and Medicine, December 1, 2006; 231(11): 1695 - 1711. [Abstract] [Full Text] [PDF]

				J. A. Clark, S. M. Doelle, M. D. Halpern, T. A. Saunders, H. Holubec, K. Dvorak, S. A. Boitano, and B. Dvorak Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G938 - G949. [Abstract] [Full Text] [PDF]

				S. M. Casalino-Matsuda, M. E. Monzon, and R. M. Forteza Epidermal Growth Factor Receptor Activation by Epidermal Growth Factor Mediates Oxidant-Induced Goblet Cell Metaplasia in Human Airway Epithelium Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 581 - 591. [Abstract] [Full Text] [PDF]

				M. D. Halpern, J. A. Clark, T. A. Saunders, S. M. Doelle, D. M. Hosseini, A. M. Stagner, and B. Dvorak Reduction of experimental necrotizing enterocolitis with anti-TNF-{alpha} Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G757 - G764. [Abstract] [Full Text] [PDF]

				R. Zamora, Y. Vodovotz, B. Betten, C. Wong, B. Zuckerbraun, K. F. Gibson, and H. R. Ford Intestinal and hepatic expression of BNIP3 in necrotizing enterocolitis: regulation by nitric oxide and peroxynitrite Am J Physiol Gastrointest Liver Physiol, November 1, 2005; 289(5): G822 - G830. [Abstract] [Full Text] [PDF]

				R. Zamora, A. Grishin, C. Wong, P. Boyle, J. Wang, D. Hackam, J. S. Upperman, K. J. Tracey, and H. R. Ford High-mobility group box 1 protein is an inflammatory mediator in necrotizing enterocolitis: protective effect of the macrophage deactivator semapimod Am J Physiol Gastrointest Liver Physiol, October 1, 2005; 289(4): G643 - G652. [Abstract] [Full Text] [PDF]