Epidermal growth factor and necrotizing enterocolitis

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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.

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      Citation Excerpt :

      Furthermore, when used in combination, EGF and another growth factor, trefoil factor, reduced the histologic colitis score in dextran-induced diarrhea by more than 40% [78], and were beneficial in indomethacin-induced gastric damage in the rat [79]. For these reasons, EGF therapy has been suggested as a possible treatment of neonatal necrotizing enterocolitis [80]. These data suggest that the EGF pathway plays an important role in repair of the inflamed colon.

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