Premium
VEGFR2 Signaling is Decreased During Necrotizing Enterocolitis
Author(s) -
Yan Xiaocai,
Liu Xueli,
Managlia Elizabeth,
De Plaen Isabelle
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1211.8
Subject(s) - necrotizing enterocolitis , fetus , cd31 , pathogenesis , hypoxia (environmental) , kinase insert domain receptor , medicine , biology , andrology , western blot , small intestine , vascular endothelial growth factor , immunohistochemistry , pathology , immunology , vascular endothelial growth factor a , vegf receptors , pregnancy , chemistry , biochemistry , genetics , organic chemistry , oxygen , gene
The pathogenesis of necrotizing enterocolitis (NEC), a common gastrointestinal disease affecting premature infants, remains poorly understood. We previously found that intestinal vascular endothelial growth factor A (VEGF‐A) expression is decreased in human NEC samples and in a neonatal mouse NEC model prior to detectable histological injury. Here we hypothesized that VEGF receptor VEGFR2 is developmentally regulated in the intestine during the perinatal period and that VEGFR2 expression and activation may be altered during NEC development. To test these hypotheses, fetal and neonatal mice of different ages (E16, 18, 20, D0, D1 and D2) were sacrificed. Also, neonatal mice were submitted to a NEC protocol consisting of adult commensal bacteria inoculation/hypoxia/cold stress/formula feeding, or allowed to be dam fed. Pups were sacrificed 24 hours later and their intestine processed for western blot analysis or immunofluorescence analysis of VEGFR2 and several cell‐type specific markers. We found that: 1) VEGFR2 protein expression significantly increases during late fetal life but decreases sharply after birth, remaining low until day of life 2, when it is significantly upregulated; 2) VEGFR2 is only detected in endothelial cells (CD31 + cells) but not in CX3CR1 + myeloid cells; 3) both VEGFR2 and pVEGFR2 are significantly decreased in the intestine of neonatal mice subjected to the NEC protocol. In conclusion, our data suggest that VEGFR2 is developmentally regulated in the perinatal intestine and VEGFR2 expression and activity are decreased during NEC development. We speculate that VEGFR2 signaling may play a critical role during NEC development. Support or Funding Information Northwestern Memorial Foundation (Friends of Prentice), NIH grants R01HD060876 (IDP)