Epidermal growth factor and necrotizing enterocolitis
Section snippets
Animal models of necrotizing enterocolitis and their relevance to human necrotizing enterocolitis
Data collected from clinical studies of NEC provide limited information about the etiology and the pathogenesis of NEC. Therefore, a relevant experimental model of NEC is essential for understanding the causes of this disease and for developing preventive therapeutic strategies. Several animal models have been developed to study the pathophysiology of NEC; these studies include pigs [12], dogs [13], rabbits [14], mice [15], and rats [16], [17], [18].
The ideal NEC model should be consistently
Maternal milk and necrotizing enterocolitis
The majority of infants with NEC (up to 95%) have been fed enterally with maternal milk or infant formula before disease onset [27]. Thus, it has been proposed that the composition of infant diet and the immaturity of GI motility, absorptive, or host defense processes contribute to the high risk and increased susceptibility of premature infants to develop NEC [28], [29]. Breast milk has been shown to have an advantage over infant formula in the reduction of human NEC [30], [31], [32], [33], [34]
Epidermal growth factor
EGF is a peptide that produces a variety of biologic responses, most of which involve regulation of cell replication, cell movement, and cell survival [49]. EGF belongs to a family of related ligands (including transforming growth factor α [TGFα]) that share amino acid sequence homology and high affinity for the same receptor—epidermal growth factor receptor (EGF-R) [50]. The biologic actions of EGF are mediated through binding to its specific receptor, EGF-R, which is distributed throughout
Role of epidermal growth factor in intestinal regeneration
Under normal physiologic conditions, the GI epithelium undergoes a continuing process of cell proliferation, differentiation, and maturation. The precise mechanisms that regulate and coordinate this rapid turnover are not known, but EGF plays an important role in this process [56]. Intestinal EGF content in suckling rats originates predominantly from milk and duodenal secretion [54], [57]. Because the expression of EGF-R in the small intestine is localized to the basolateral compartment of
Role of epidermal growth factor in necrotizing enterocolitis
The first report relating EGF and intestinal necrosis in humans was reported in England [75]. A critically ill 8-month-old child with intestinal necrosis similar to NEC was treated with continuous infusion of EGF. Within 4 days of EGF treatment, the severely damaged intestinal structure was recovered and healed [75]. Scott et al [76] have shown increased urinary EGF levels in neonates diagnosed with NEC, and they have speculated that elevated urinary EGF levels might result from increased
Mechanisms of epidermal growth factor protection in necrotizing enterocolitis
The involvement of the EGF receptor in the biologic actions of EGF in the developing GI tract is well established [55]. Originally, EGF-R expression was thought to be localized only at the basolateral membrane of the crypt and villus epithelium [58], [59], [60], [81]. However, recent studies have shown the presence of EGF-R on the apical membrane of villus epithelium [22], [82], [83]. The expression of EGF-R is detected in intestinal epithelium of infants with necrotizing enterocolitis [84].
Summary
As the number of extremely low-birth-weight infants increases, NEC remains a critical eminent problem [88]. Supplementation of enteral feeds with biologically active substances normally present in breast milk, such as EGF, seems to be a logical and safe way to reduce the incidence of intestinal inflammation and NEC. Continuing basic research and clinical studies are essential before EGF can be introduced as an efficient therapeutic approach in the treatment of neonatal NEC.
Acknowledgements
This work was supported by the National Institute of Child Health and Human Development Grant HD39657.
References (88)
Necrotizing enterocolitis: the search for a unifying pathogenic theory leading to prevention
Pediatr Clin North Am
(1996)- et al.
Necrotizing enterocolitis in term infants
J Pediatr
(1976) - et al.
Necrotizing enterocolitis in very low birth weight infants: biodemographic and clinical correlates. National Institute of Child Health and Human Development Neonatal Research Network
J Pediatr
(1991) - et al.
Necrotizing enterocolitis in full-term infants
J Pediatr Surg
(2003) - et al.
A mouse model for the study of necrotizing enterocolitis
J Pediatr Surg
(1986) - et al.
Necrotizing enterocolitis: role of platelet activating factor, endotoxin, and tumor necrosis factor
J Pediatr
(1990) - et al.
Bifidobacterial supplementation reduces the incidence of necrotizing enterocolitis in a neonatal rat model
Gastroenterology
(1999) - et al.
Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitis
J Pediatr
(1990) - et al.
An experimental study of acute neonatal enterocolitis: the importance of breast milk
J Pediatr Surg
(1974) Epidemiology of necrotizing enterocolitis
Clin Perinatol
(1994)
Breast milk and neonatal necrotising enterocolitis
Lancet
The use of human milk for premature infants
Pediatr Clin North Am
Host defense mechanisms of human milk and their relations to enteric infections and necrotizing enterocolitis
Clin Perinatol
Search for role of milk-borne biologically active peptides for the suckling
J Nutr
Heparin-binding EGF-like growth factor is present in human amniotic fluid and breast milk
J Pediatr Surg
Epidermal growth factor-like proteins in breast fluid and human milk
Life Sci
Epidermal growth factor in human milk: daily production and diurnal variation during early lactation in mothers delivering at term and at premature gestation
J Pediatr
Transforming growth factor (TGF)-alpha in human milk
Life Sci
EGF receptor ligands
Exp Cell Res
Epidermal growth factor
J Invest Dermatol
Epidermal growth factor (EGF)
Baillieres Clin Gastroenterol
Epidermal growth factor and transforming growth factor-alpha mRNA in rat small intestine: in situ hybridization study
FEBS Lett
Developmental regulation of epidermal growth factor receptor kinase in rat intestine
Gastroenterology
Gastric cytoprotection by epidermal growth factor: role of endogenous prostaglandins and DNA synthesis
Gastroenterology
Increased production of transforming growth factor alpha following acute gastric injury
Gastroenterology
A defective EGF-receptor in waved-2 mice attenuates intestinal adaptation
J Surg Res
Adaptation after small bowel resection is attenuated by sialoadenectomy: the role for endogenous epidermal growth factor
Surgery
The distribution of endogenous epidermal growth factor after small bowel resection suggests increased intestinal utilization during adaptation
J Pediatr Surg
Epidermal growth factor receptor expression following small bowel resection
J Surg Res
The effect of epidermal growth factor on differentiation of isolated enterocytes after small bowel resection
J Pediatr Surg
Epidermal growth factor in necrotising enteritis
Lancet
Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders
Am J Clin Nutr
Epidermal growth factor receptor of the intestinal enterocyte: localization to laterobasal but not brush border membrane
J Biol Chem
Expression of EGF and ERBB receptor proteins in small intestinal epithelium
Gastroenterology
Immunoreactive epidermal growth factor receptors are present in gastrointestinal epithelial cells of preterm infants with necrotising enterocolitis
Early Hum Dev
Interleukin-10-deficient mice develop chronic enterocolitis
Cell
Neonatal necrotizing enterocolitis, a disease of the immature intestinal mucosal barrier
Acta Paediatr Suppl
Neonatal necrotizing enterocolitis: an overview
Curr Opin Infect Dis
Very low birth weight outcomes of the National Institute of Child health and human development neonatal research network, January 1995 through December 1996. NICHD Neonatal Research Network
Pediatrics
Neonatal necrotizing enterocolitis: a nine-year experience: II. Outcome assessment
Am J Dis Child
New concepts in necrotizing enterocolitis
Curr Opin Pediatr
Necrotizing enterocolitis: a review of pathogenetic mechanisms and implications for prevention
Pediatr Pathol
Feeding strategies for premature infants: beneficial outcomes of feeding fortified human milk versus preterm formula
Pediatrics
Characterization of intestinal collateral blood flow in the developing piglet
Pediatr Res
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