PC.17 Impaired mucosal restitution in neonatal necrotising enterocolitis

Abstract

Background The aetiology of necrotizing enterocolitis (NEC) is multifactorial and its pathogenesis poorly understood. The trefoil factor peptides (TFF1–3) contribute to protective mechanisms operating in the gastro-intestinal (GI) mucosa and play a fundamental role in epithelial protection, restitution and repair. The role of TFF1–3 in neonatal mucosal protection has not been well investigated. Aims This study aims to investigate alterations in TFF 13 mRNA and protein expression in the GI tract of infants with NEC compared to normal neonatal controls. Methods Bowel resection specimens were collected with parental consent from neonates undergoing laparotomy. In situ hybridisation, real time PCR and immunohistochemistry were performed to examine trefoil mRNA and peptide expression in the neonatal GI tract. Results 77 neonatal bowel specimens were examined (NEC n = 27, recovering from NEC n = 16, normal neonatal controls n = 29). There was no upregulation of TFF 1 and 2 mRNA and protein expression in acute NEC and there was significant down-regulation of TFF3 protein and mRNA expression. Adjacent to areas of mucosal necrosis there was an inverse relationship in the number of TFF3-positive goblet cells and proximity to the ulceration. Conclusions A number of studies have shown up-regulation of TFF 1–3 in the acute phase response to GI mucosal injury, promotion of epithelial cell migration and protection against apoptosis. Our results suggest a lack of TFF expression in response to NEC in the premature gut. This may lead to impaired restitution of the mucosa and contribute to the cascade of bowel necrosis and generalised sepsis characteristic of NEC.