Heparin-binding Epidermal Growth Factor-like Growth Factor Overexpression in Transgenic Mice Increases Resistance to Necrotizing Enterocolitis

Overview

Journal J Pediatr Surg

Specialties General Surgery
Pediatrics

Date 2010 Oct 6

PMID 20920709

Citations 26

Authors

Andrei Radulescu

Hong-Yi Zhang

Xiaoyi Yu

Jacob K Olson

Amanda K Darbyshire

Yan Chen

Gail E Besner

Affiliations

Soon will be listed here.

Abstract

Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency and the leading surgical cause of death in premature infants. We have shown that administration of exogenous heparin-binding epidermal growth factor-like growth factor (HB-EGF) in mice protects the intestines from experimental NEC. The aim of the current study was to evaluate the effect of gain-of-function of endogenous HB-EGF on susceptibility to NEC.

Methods: Neonatal HB-EGF transgenic (TG) mice and their wild-type (WT) counterparts were exposed to experimental NEC. An additional group of HB-EGF TG pups were also exposed to NEC, but received the HB-EGF antagonist cross-reacting material 197 (CRM197) injected subcutaneously immediately after birth. To examine gut barrier function, HB-EGF TG and WT pups received intragastric fluorescein isothiocyanate-labeled dextran under basal and stressed conditions, and serum fluorescein isothiocyanate-labeled dextran levels were measured.

Results: Wild-type mice had an incidence of NEC of 54.2%, whereas HB-EGF TG mice had a significantly decreased incidence of NEC of 22.7% (P = .03). Importantly, administration of CRM197 to HB-EGF TG pups significantly increased the incidence of NEC to 65% (P = .004). HB-EGF TG mice had significantly decreased intestinal permeability compared to WT mice both under basal and stressed conditions.

Conclusions: Our results provide evidence that overexpression of the HB-EGF gene decreases susceptibility to NEC and that administration of the HB-EGF antagonist CRM197 reverses this protective effect.

Citing Articles

Animal models of necrotizing enterocolitis.

Mendez Y, Khan F, Van Perrier G, Radulescu A World J Pediatr Surg. 2022; 3(1):e000109.

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Prenatal administration of heparin-binding epidermal growth factor-like growth factor in an experimental model of necrotizing enterocolitis decreased both incidence and severity of the disease.

Sacks M, Mendez Y, Khan F, Propst R, Zuppan C, Wilson C World J Pediatr Surg. 2022; 5(1):e000345.

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Prenatal stress increases IgA coating of offspring microbiota and exacerbates necrotizing enterocolitis-like injury in a sex-dependent manner.

Brawner K, Yeramilli V, Kennedy B, Patel R, Martin C Brain Behav Immun. 2020; 89:291-299.

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Saccharomyces boulardii modulates necrotizing enterocolitis in neonatal mice by regulating the sirtuin 1/NF‑κB pathway and the intestinal microbiota.

Zhang K, Zhang X, Lv A, Fan S, Zhang J Mol Med Rep. 2020; 22(2):671-680.

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Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants.

Gopalakrishna K, Macadangdang B, Rogers M, Tometich J, Firek B, Baker R Nat Med. 2019; 25(7):1110-1115.

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