ArticlePloS one2016
Vascular Endothelial Growth Factor (VEGF) Bioavailability Regulates Angiogenesis and Intestinal Stem and Progenitor Cell Proliferation during Postnatal Small Intestinal Development.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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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.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
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- Dynamic changes in BDNF, VEGF, and GDNF after transplanting human protein-based scaffolds with Wharton's Jelly MSCs in a rat brain injury model.Scientific reports · 2025Article
- Daikenchuto improves methotrexate-induced chronic small intestinal mucositis by promoting angiogenesis.Frontiers in pharmacology · 2025Article
- Integration of Stromal Cells and Hydrogel Below Epithelium Results in Optimal Barrier Properties of Small Intestine Organoid Models.Biomedicines · 2024Article
- p16Immunity & ageing : I & A · 2024Article
- Modulation of the intestinal mucosal and cell-mediated response against natural helminth infection in the African catfish Clarias gariepinus.BMC veterinary research · 2024Article
- Investigation of Gastrointestinal Toxicities Associated with Concurrent Abdominal Radiation Therapy and the Tyrosine Kinase Inhibitor Sunitinib in a Mouse Model.International journal of molecular sciences · 2024Article
- Mechanisms and functions of intestinal vascular specialization.The Journal of experimental medicine · 2024Review
- Role of Hypoxic Secretome from Mesenchymal Stem Cells in Enhancing Tissue Repair: Regulatory Effects on HIF-1α, VEGF, and Fibroblast in a Sphincterotomy Rat Model.Journal of inflammation research · 2024Article
- Sinensetin suppresses angiogenesis in liver cancer by targeting the VEGF/VEGFR2/AKT signaling pathway.Experimental and therapeutic medicine · 2022Article
- Prenatal over- and undernutrition differentially program small intestinal growth, angiogenesis, absorptive capacity, and endocrine function in sheep.Physiological reports · 2020Article
- Secretome of Senescent Adipose-Derived Mesenchymal Stem Cells Negatively Regulates Angiogenesis.International journal of molecular sciences · 2020Article
- Patient-derived small intestinal myofibroblasts direct perfused, physiologically responsive capillary development in a microfluidic Gut-on-a-Chip Model.Scientific reports · 2020Article
- Hypoxic Preconditioning Enhances Survival and Proangiogenic Capacity of Human First Trimester Chorionic Villus-Derived Mesenchymal Stem Cells for Fetal Tissue Engineering.Stem cells international · 2019Article
- Analysis of changes to lncRNAs and their target mRNAs in murine jejunum after radiation treatment.Journal of cellular and molecular medicine · 2018Article
- Lacteal junction zippering protects against diet-induced obesity.Science (New York, N.Y.) · 2018Article
- P18 peptide, a functional fragment of pigment epithelial-derived factor, inhibits angiogenesis in hepatocellular carcinoma via modulating VEGF/VEGFR2 signalling pathway.Oncology reports · 2017Article
- Revision of the concept of anti-angiogenesis and its applications in tumor treatment.Chronic diseases and translational medicine · 2017Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVascular endothelial growth factor (VEGF) is a highly conserved, master regulatory molecule required for endothelial cell proliferation, organization, migration and branching morphogenesis. Podocoryne carnea and drosophila, which lack endothelial cells and a vascular system, express VEGF homologs, indicating potential roles beyond angiogenesis and vasculogenesis. The role of VEGF in the development and homeostasis of the postnatal small intestine is unknown. We hypothesized regulating VEGF bioavailability in the postnatal small intestine would exhibit effects beyond the vasculature and influence epithelial cell stem/progenitor populations.
methodsVEGF mutant mice were created that overexpressed VEGF in the brush border of epithelium via the villin promotor following doxycycline treatment. To decrease VEGF bioavailability, sFlt-1 mutant mice were generated that overexpressed the soluble VEGF receptor sFlt-1 upon doxycycline administration in the intestinal epithelium. Mice were analyzed after 21 days of doxycycline administration.
resultsIncreased VEGF expression was confirmed by RT-qPCR and ELISA in the intestine of the VEGF mutants compared to littermates. The VEGF mutant duodenum demonstrated increased angiogenesis and vascular leak as compared to littermate controls. The VEGF mutant duodenum revealed taller villi and increased Ki-67-positive cells in the transit-amplifying zone with reduced Lgr5 expression. The duodenum of sFlt-1 mutants revealed shorter villi and longer crypts with reduced proliferation in the transit-amplifying zone, reduced expression of Dll1, Bmp4 and VE-cadherin, and increased expression of Sox9 and EphB2.
conclusionsManipulating VEGF bioavailability leads to profound effects on not only the intestinal vasculature, but epithelial stem and progenitor cells in the intestinal crypt. Elucidation of the crosstalk between VEGF signaling in the vasculature, mesenchyme and epithelial stem/progenitor cell populations may direct future cell therapies for intestinal dysfunction or disease.
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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.