Evidence map›Paper›PMID 29068435›Full record

ArticlePediatric research2018

Dimethyloxalylglycine preserves the intestinal microvasculature and protects against intestinal injury in a neonatal mouse NEC model: role of VEGF signaling.

Rakhee M Bowker, Xiaocai Yan, Elizabeth Managlia, Shirley X L Liu, Catherine Marek, Xiao-Di Tan, Isabelle G De Plaen

Open access · bronzeAbstract read
In one paragraph

Article in Pediatric research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 27 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Rakhee M BowkerDivision of Neonatology, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
Xiaocai YanDivision of Neonatology, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
Elizabeth ManagliaDivision of Neonatology, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
Shirley X L LiuDivision of Neonatology, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
Catherine MarekDivision of Neonatology, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
Xiao-Di TanCenter for Intestinal and Liver Inflammation Research, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, Illinois.
Isabelle G De PlaenDivision of Neonatology, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
Northwestern University · USLurie Children's Hospital · US

Funding

Preservation of mucosal barrier in surgical diseasesR01DK064240 · NIDDK · LURIE CHILDREN'S HOSPITAL OF CHICAGO · PI TAN, XIAO-DI · 2004 to 2014
$3.0M
Surgical studies of gut epithelial apoptosis-initiated critical illnessR01GM117628 · NIGMS · LURIE CHILDREN'S HOSPITAL OF CHICAGO · PI TAN, XIAO-DI · 2016 to 2019
$1.9M
Cell-specific role of NF-KB in necrotizing enterocolitisR01HD060876 · NICHD · LURIE CHILDREN'S HOSPITAL OF CHICAGO · PI DE PLAEN, ISABELLE G · 2010 to 2014
$1.5M
NICHD NIH HHS R01 HD060876NIDDK NIH HHS R01 DK064240NIGMS NIH HHS R01 GM117628
6 · The paper itself

Abstract

BackgroundNecrotizing enterocolitis (NEC) is a devastating neonatal disease characterized by intestinal necrosis. Hypoxia-inducible factor-1α (HIF-1α) has a critical role in cellular oxygen homeostasis. Here, we hypothesized that prolyl hydroxylase (PHD) inhibition, which stabilizes HIF-1α, protects against NEC by promoting intestinal endothelial cell proliferation and improving intestinal microvascular integrity via vascular endothelial growth factor (VEGF) signaling.MethodsTo assess the role of PHD inhibition in a neonatal mouse NEC model, we administered dimethyloxalylglycine (DMOG) or vehicle to pups before or during the NEC protocol, and determined mortality and incidence of severe intestinal injury. We assessed intestinal VEGF by western blot analysis and quantified endothelial cell and epithelial cell proliferation following immunofluorescence.ResultsDMOG decreased mortality and incidence of severe NEC, increased intestinal VEGF expression, and increased intestinal villus endothelial and epithelial cell proliferation in experimental NEC. Inhibiting VEGFR2 signaling eliminated DMOG's protective effect on intestinal injury severity, survival, and endothelial cell proliferation while sparing DMOG's protective effect on intestinal epithelial cell proliferation.ConclusionDMOG upregulates intestinal VEGF, promotes endothelial cell proliferation, and protects against intestinal injury and mortality in experimental NEC in a VEGFR2 dependent manner. DMOG's protective effect on the neonatal intestinal mucosa may be mediated via VEGFR2 dependent improvement of the intestinal microvasculature.

Indexed as

MicrocirculationAmino Acids, DicarboxylicAnimalsAnimals, NewbornCell ProliferationDisease Models, AnimalEndothelial CellsEnterocolitis, NecrotizingHypoxia-Inducible Factor 1, alpha SubunitIntestinesMiceMice, Inbred C57BLProlyl HydroxylasesSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Amino Acids, DicarboxylicHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitKdr protein, mouseoxalylglycineProlyl HydroxylasesVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2

Identifiers

PMID29068435
PMCPMC5866158
OpenAlexW2755600999

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.