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

Mubina Isani, Laura Illingworth, Eliot M Herman, Monica Schmidt, Lauren Barron, Jordan Bowling, Melissa Elizee, Iris Bai, Christopher Gayer, Anatoly Grishin, Christopher R. Erwin, Henri R. Ford, Brad W. Warner

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 150 μg/kg/day EGF caused considerable mortality, whereas those corresponding to 75 μg/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 75 μg/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.

Original languageEnglish (US)
JournalJournal of Pediatric Surgery
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Necrotizing Enterocolitis
Soybeans
Epidermal Growth Factor
Zonula Occludens-1 Protein
Tight Junction Proteins
Costs and Cost Analysis
Messenger RNA
Fluorescent Antibody Technique
Real-Time Polymerase Chain Reaction
Pathology

Keywords

  • EGF
  • Necrotizing enterocolitis
  • Prophylaxis
  • Soybean

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

Cite this

Soybean-derived recombinant human epidermal growth factor protects against experimental necrotizing enterocolitis. / Isani, Mubina; Illingworth, Laura; Herman, Eliot M; Schmidt, Monica; Barron, Lauren; Bowling, Jordan; Elizee, Melissa; Bai, Iris; Gayer, Christopher; Grishin, Anatoly; Erwin, Christopher R.; Ford, Henri R.; Warner, Brad W.

In: Journal of Pediatric Surgery, 01.01.2018.

Research output: Contribution to journalArticle

Isani, Mubina ; Illingworth, Laura ; Herman, Eliot M ; Schmidt, Monica ; Barron, Lauren ; Bowling, Jordan ; Elizee, Melissa ; Bai, Iris ; Gayer, Christopher ; Grishin, Anatoly ; Erwin, Christopher R. ; Ford, Henri R. ; Warner, Brad W. / Soybean-derived recombinant human epidermal growth factor protects against experimental necrotizing enterocolitis. In: Journal of Pediatric Surgery. 2018.
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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 150 μg/kg/day EGF caused considerable mortality, whereas those corresponding to 75 μg/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 75 μg/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.",
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AU - Elizee, Melissa

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AB - 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 150 μg/kg/day EGF caused considerable mortality, whereas those corresponding to 75 μg/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 75 μg/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.

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