Soybean-derived recombinant human epidermal growth factor protects against experimental necrotizing enterocolitis

J Pediatr Surg. 2018 Jun;53(6):1203-1207. doi: 10.1016/j.jpedsurg.2018.02.084. Epub 2018 Mar 8.

Abstract

Background: Epidermal Growth Factor (EGF) reduces necrotizing enterocolitis (NEC). However, its high cost virtually prohibits clinical use. To reduce cost, soybean expressing human EGF was developed. Here we report effectiveness of soybean-derived EGF in experimental NEC.

Methods: Newborn rats were subjected to the NEC-inducing regimen of formula feeding and hypoxia. Formula was supplemented with extract from EGF-expressing or empty soybeans. NEC pathology was determined microscopically. Localization of tight junction proteins JAM-A and ZO-1 was examined by immunofluorescence and levels of mucosal COX-2 and iNOS mRNAs by real time PCR.

Results: Soybean extract amounts corresponding to 150μg/kg/day EGF caused considerable mortality, whereas those corresponding to 75μg/kg/day EGF were well tolerated. There was no significant difference in NEC scores between animals fed plain formula and formula supplemented with empty soybean extract. Soybean-EGF-supplemented formula at 75μg/kg/day EGF significantly decreased NEC, attenuated dissociation of JAM-A and ZO-1 proteins from tight junctions, and reduced intestinal expression of COX-2 and iNOS mRNAs.

Conclusion: Supplementation with soybean-expressed EGF significantly decreased NEC in the rat model. Soybean-expressed EGF may provide an economical solution for EGF administration and prophylaxis of clinical NEC.

Keywords: EGF; Necrotizing enterocolitis; Prophylaxis; Soybean.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cyclooxygenase 2 / metabolism
  • Disease Models, Animal
  • Enterocolitis, Necrotizing / pathology
  • Enterocolitis, Necrotizing / prevention & control*
  • Epidermal Growth Factor / therapeutic use*
  • Glycine max*
  • Humans
  • Infant Formula
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / pathology
  • Infant, Premature, Diseases / prevention & control
  • Intestinal Mucosa / metabolism
  • Intestines / pathology
  • Junctional Adhesion Molecules / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Extracts / therapeutic use*
  • Protective Agents / therapeutic use*
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Recombinant Proteins / therapeutic use
  • Zonula Occludens Proteins / metabolism

Substances

  • Junctional Adhesion Molecules
  • Plant Extracts
  • Protective Agents
  • RNA, Messenger
  • Recombinant Proteins
  • Zonula Occludens Proteins
  • Epidermal Growth Factor
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Ptgs2 protein, rat