Heparin-binding EGF-like growth factor promotes neuronal nitric oxide synthase expression and protects the enteric nervous system after necrotizing enterocolitis.
Pediatr Res
; 82(3): 490-500, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28422949
ABSTRACT
BackgroundNeonatal necrotizing enterocolitis (NEC) is associated with alterations of the enteric nervous system (ENS), with loss of neuronal nitric oxide synthase (nNOS)-expressing neurons in the intestine. The aim of this study was to investigate the roles of heparin-binding EGF-like growth factor (HB-EGF) in neural stem cell (NSC) differentiation, nNOS expression, and effects on ENS integrity during experimental NEC.MethodsThe effects of HB-EGF on NSC differentiation and nNOS production were determined using cultured enteric NSCs. Myenteric neuronal subpopulations were examined in HB-EGF knockout mice. Rat pups were exposed to experimental NEC, and the effects of HB-EGF treatment on nNOS production and intestinal neuronal apoptosis were determined.ResultsHB-EGF promotes NSC differentiation, with increased nNOS production in differentiated neurons and glial cells. Moreover, loss of nNOS-expressing neurons in the myenteric plexus and impaired neurite outgrowth were associated with absence of the HB-EGF gene. In addition, administration of HB-EGF preserves nNOS expression in the myenteric plexus and reduces enteric neuronal apoptosis during experimental NEC.ConclusionHB-EGF promotes the differentiation of enteric NSCs into neurons in a nitric oxide (NO)-dependent manner, and protects the ENS from NEC-induced injury, providing new insights into potential therapeutic strategies for the treatment of NEC in the future.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistema Nervoso Entérico
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Enterocolite Necrosante
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Óxido Nítrico Sintase Tipo I
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Fator de Crescimento Semelhante a EGF de Ligação à Heparina
Limite:
Animals
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Pregnancy
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article