6.9 Up-regulation and shift in cellular and tissue localisation of Epidermal Growth Factor Receptor in Acute Necrotising Enterocolitis

Abstract

Background The pivotal role of epidermal growth factor receptor (EGFR) in transducing signalling by multiple ligands involved in proliferation, differentiation and migration is evidenced by the fact that EGFR-null mice invariably die in utero or early post-natal life. Inactivation of EGFR in knockout mice results in a haemorrhagic enterocolitis similar to necrotising enterocolitis (NEC). Aims This study aims to define the pattern of expression and localisation of the EGFR in foetal bowel, normal neonatal gastrointestinal tract (GIT) and in NEC. Methods Foetal bowel samples and bowel resection specimens from neonates undergoing laparotomy were collected with parental consent. Immunohistochemistry was performed to examine EGFR expression and localisation in the GI tract. Results 15 foetal and 58 neonatal bowel specimens were examined (NEC n = 22, recovering from NEC n = 12, normal neonatal controls n = 24). EGFR was detected in all foetal bowel samples from 10+3 weeks gestation and was localised to the apical membrane of GI epithelial cells. In acute NEC an increase in EGFR expression and a partial shift in localisation to the apical surface of GI epithelial cells was observed when compared to normal neonatal controls. Conclusions It has been proposed that EGFR forms part of an essential defence mechanism of intestinal epithelial integrity, wherein peptide growth factors play critical protective and reparative roles. This study demonstrates apical expression of EGFR protein in the GI epithelium during acute NEC, which may enhance the ability of luminally delivered growth factors and protective peptides to exert their restitutive effects in acute mucosal injury.