ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2016
Lack of VEGFR2 signaling causes maldevelopment of the intestinal microvasculature and facilitates necrotizing enterocolitis in neonatal mice.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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.
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.
Who cites it
39 citing papers in PubMed, 59 citations in OpenAlex.
- rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial.The Journal of pediatrics · 2019Trial
- Endothelial VEGFR-2 Activation Precedes Severe Mucosal Injury in TNBS-Induced Colitis.International journal of molecular sciences · 2026Article
- Necrotizing enterocolitis.Nature reviews. Disease primers · 2026Review
- Pathogenesis of necrotizing enterocolitis: mechanisms and mediators.World journal of pediatric surgery · 2026Review
- Digging deeper into necrotizing enterocolitis: bridging clinical, microbial, and molecular perspectives.Gut microbes · 2025Review
- Epigenetics in neonatal necrotizing enterocolitis: current understanding and the potential involvement of m6A modification.Frontiers in pediatrics · 2025Review
- Microbiota regulates neonatal disease tolerance to virus-evoked necrotizing enterocolitis by shaping the STAT1-NLRC5 axis in the intestinal epithelium.Cell host & microbe · 2024Article
- Recombinant IGF-1/BP3 protects against intestinal injury in a neonatal mouse NEC model.Pediatric research · 2024Article
- Mechanisms and functions of intestinal vascular specialization.The Journal of experimental medicine · 2024Review
- Nailfold Capillaroscopy: A Promising, Noninvasive Approach to Predict Retinopathy of Prematurity.The Journal of pediatrics · 2023Article
- Association of Surgical Necrotizing Enterocolitis and Its Timing with Retinopathy of Prematurity.American journal of perinatology · 2023Article
- Endothelial FOXC1 and FOXC2 promote intestinal regeneration after ischemia-reperfusion injury.EMBO reports · 2023Article
- Necrotizing enterocolitis: recent advances in treatment with translational potential.Pediatric surgery international · 2023Review
- Genetic Polymorphisms of Vascular Endothelial Growth Factor in Neonatal Pathologies: A Systematic Search and Narrative Synthesis of the Literature.Children (Basel, Switzerland) · 2023Review
- Necrotizing enterocolitis in premature infants-A defect in the brakes? Evidence from clinical and animal studies.Mucosal immunology · 2023Review
- State-of-the-art review and update ofFrontiers in pediatrics · 2023Review
- Study on the mechanism of Wumei San in treating piglet diarrhea using network pharmacology and molecular docking.Frontiers in veterinary science · 2023Article
- Feeding mode influences dynamic gut microbiota signatures and affects susceptibility to anti-CD3 mAb-induced intestinal injury in neonatal mice.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Bench to bedside - new insights into the pathogenesis of necrotizing enterocolitis.Nature reviews. Gastroenterology & hepatology · 2022Review
- Advances in our understanding of the molecular pathogenesis of necrotizing enterocolitis.BMC pediatrics · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The pathogenesis of necrotizing enterocolitis (NEC), a common gastrointestinal disease affecting premature infants, remains poorly understood. We previously found that intestinal VEGF-A expression is decreased in human NEC samples and in a neonatal mouse NEC model prior to detectable histological injury. Therefore, we hypothesized that lack of VEGF receptor 2 (VEGFR2) signaling facilitates neonatal intestinal injury by impairing intestinal microvasculature development. Here, we found that intestinal VEGF-A and its receptor, VEGFR2, were highly expressed at the end of fetal life and significantly decreased after birth in mice. Furthermore, selective inhibition of VEGFR2 kinase activity and exposure to a neonatal NEC protocol significantly decreased the density of the intestinal microvascular network, which was further reduced when both interventions were provided together. Furthermore, VEGFR2 inhibition resulted in greater mortality and incidence of severe injury in pups submitted to the NEC model. The percentage of lamina propria endothelial cells was decreased during NEC induction, and further decreased when VEGFR2 signaling was inhibited. This was associated with decreased endothelial cell proliferation rather than apoptosis. In conclusion, we found that VEGF-A and VEGFR2 proteins are highly expressed in the intestine before birth, and are significantly downregulated in the immediate neonatal period. Furthermore, VEGFR2 signaling is necessary to maintain the integrity of the intestinal mucosal microvasculature during the postnatal period and lack of VEGFR2 signaling predisposes to NEC in neonatal mice.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.