The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Vascular Endothelial Growth Factor Has Neurotrophic Activity and Stimulates Axonal Outgrowth, Enhancing Cell Survival and Schwann Cell Proliferation in the Peripheral Nervous System
Open accessAbstract
Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells, and it promotes angiogenesis in vivo. Here we report that VEGF 165 has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG) and dorsal root ganglia (DRG), measured as axonal outgrowth. Maximal effect was observed at 10–50 ng/ml for SCG and 100 ng/ml for DRG. VEGF-induced axonal outgrowth was inhibited by the mitogen-activated protein kinase kinase inhibitor PD 98059 but not by the protein kinase inhibitor K252a. VEGF also increased survival of both neurons and satellite cells and the number of proliferating Schwann cells. Immunocytochemistry and immunoblotting revealed that VEGF was expressed in virtually all nerve cells in the SCG but only in a population of small-diameter (<35 μm) neurons representing ∼30% of the neurons in DRG. Immunostaining showed that the VEGF receptor fetal liver kinase receptor (flk-1) was found on nerve cell bodies in DRG and to a lesser extent on neurons in SCG. Growth cones of regenerating axons from both types of ganglia exhibited flk-1 immunoreactivity, as did Schwann cells. We conclude that VEGF has both neurotrophic and mitogenic activity on cells in the peripheral nervous system.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Vascular endothelial growth factor (VEGF) is known to promote revascularization, axonal outgrowth, and Schwann cell proliferation.58”
From Regenerative Electrode Interfaces for Neural Prostheses. (2016) · cites this paper as [58]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · cited 2×
“The samples were electrophoresed according to Laemmli (1970).”
MethodRaza, H., John, A., & Nemmar, A. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350087 · Cited by 47,311
The Biology of Vascular Endothelial Growth Factor
Ferrara, N., & Davis-Smyth, T. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.1.0287 · Cited by 4,585
Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice
Shalaby, F., Rossant, J., Yamaguchi, T. P., Gertsenstein, M., Wu, X.-F., Breitman, M. L., & Schuh, A. C. (1995) · Nature · doi:10.1038/376062a0 · Cited by 3,931 · cited 2×
“Both receptor types are essential for development and organization of endothelial cells and the disruption of the genes encoding flk-1 and flt-1 results in defects of blood vessel formation and an early death of homozygous mice embryo (Fong et al., 1995; Shalaby et al., 1995 ).”
BackgroundRole of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium
Fong, G.-H., Rossant, J., Gertsenstein, M., & Breitman, M. L. (1995) · Nature · doi:10.1038/376066a0 · Cited by 2,606 · cited 1×
“Both receptor types are essential for development and organization of endothelial cells and the disruption of the genes encoding flk-1 and flt-1 results in defects of blood vessel formation and an early death of homozygous mice embryo (Fong et al., 1995; Shalaby et al., 1995).”
BackgroundSöker, S., Takashima, S., Miao, H. Q., Neufeld, G., & Klagsbrun, M. (1998) · Cell · doi:10.1016/s0092-8674(00)81402-6 · Cited by 2,493 · cited 2×
“It has also been reported that VEGF165 binds to neurophilin-1 ( Soker et al., 1998 ), a neuronal cell surface molecule that is important for chemorepulsive signaling during peripheral axonal outgrowth in the developing mice (Kitsukawa et al., 1997).”
BackgroundVascular Permeability Factor, an Endothelial Cell Mitogen Related to PDGF
Keck, P. J., Hauser, S. D., Krivi, G. G., Sanzo, K., Warren, T. G., Feder, J., & Connolly, D. T. (1989) · Science · doi:10.1126/science.2479987 · Cited by 2,058 · cited 2×
“However, other angiogenic factors, including basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF), have been shown to be neurotrophic or exert growthpromoting activity (Rydel and Greene, 1987; Davis and Stroobant, 1990; Smits et al., 1991; Fujimoto et al., 1997).”
BackgroundThe fms -Like Tyrosine Kinase, a Receptor for Vascular Endothelial Growth Factor
de Vries, C. J. M., Escobedo, J. A., Ueno, H., Houck, K. A., Ferrara, N., & Williams, L. T. (1992) · Science · doi:10.1126/science.1312256 · Cited by 2,019 · cited 2×
“VEGF exerts its action via high-affinity binding to two types of phosphotyrosine kinase receptors: fms-like tyrosine kinase (flt-1) and fetal liver kinase receptor (flk-1) (De Vries et al., 1992; Quinn et al., 1993).”
BackgroundWaltenberger, J. L., Claesson, L., Siegbahn, A., Shibuya, M., & Heldin, C. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47116-5 · Cited by 1,661 · cited 2×
“The human counterpart to the flk-1 receptor, which activates the mitogen-activated protein kinase (MAPK) pathway, is also known to induce reorganization of actin filaments, chemotaxis, and give rise to a mitogen response in endothelial cells (Waltenberger et al., 1994; Kroll and Waltenberger, 1997).”
BackgroundMolecular and Biological Properties of the Vascular Endothelial Growth Factor Family of Proteins
Ferrara, N., Houck, K. A., Jakeman, L. B., & LEUNG, D. W. (1992) · Endocrine Reviews · doi:10.1210/edrv-13-1-18 · Cited by 1,655 · cited 1×
“In the nervous system, VEGF mRNA has been found in neurons in the capillary-rich areas of the brain, for instance in the pars distalis cells of the pituitary gland but also in glial cells in the retina after hypoxia (Ferrara et al., 1992; Stone et al., 1995).”
Background
Cited by
Sorted by citations
Items 701–750 of 750
Paviour, D. C., & Ellis, C. (2008) · Cephalalgia · doi:10.1111/j.1468-2982.2008.01669.x
Pathophysiology and Clinical Implications of Vascular Endothelial Growth Factor
Ferrara, N. (2007) · Springer eBooks · doi:10.1007/978-3-540-33177-3_5
de Oliveira, G. P. (2014) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2014.tde-06062014-101803
Microneurovascular free muscle transfer with cross-over nerve grafts in facial reanimation
Ylä-Kotola, T. M. (2008) · Työväentutkimus Vuosikirja
Molecular mechanisms of lymphangiogenesis: role of VEGFR-3 mediated signaling
Mäkinen, T. (2002) · Työväentutkimus Vuosikirja
Vieira, J. J. (2014) · The Atrium (University of Guelph)
Oliveira‐Giacomelli, Á. (2014)
MacMillan, C. J. (2013) · Library and Archives Canada (Government of Canada)
Consequences of Intracellular Amyloid in Vascular System
D’Andrea, M. R. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-804256-4.00008-5
Lasso, J. M., Prieto, J., & Fernández‐Santos, M. E. (2015) · Recent Patents on Regenerative Medicine · doi:10.2174/2210296505666150120215128
“Gene therapy with AAV is an effective approach to reach the regeneration of the peripheral nerve as AAVs have been tested to deliver efficiently new porangiogenic genes to nerves which help to induce neural repair in experimental models [89].”
MethodKolar, M. K. (2016) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Sebben, A. D., Cocolichio, F. M., Schmitt, A. P. V., Curra, M. D., Tres, G. L., & Silva, J. B. (2011) · DOAJ (DOAJ: Directory of Open Access Journals)
Butler, S. M., Williams, J. M., Khorram, O., Pearce, W. J., Hubbell, M. C., Semotiuk, A., Thorpe, R. B., & Adeoye, O. O. (2016)
VEGF, an Angiogenic Factor with Neurotrophic Activity, Useful for Treatment of ALS?
Lambrechts, D., & Carmeliet, P. (2006) · Elsevier eBooks · doi:10.1016/b978-012397632-1/50020-4
Angiogenic Factors and Inhibitors
Tolentino, M. J., Adamis, A. P., & Miller, J. W. (2008) · Elsevier eBooks · doi:10.1016/b978-1-4160-0016-7.50034-5
Sofolahan, S. (2010) · SHAREOK (University of Oklahoma; Oklahoma State University; Central Oklahoma University)
Real-Time Imaging of Accessible Axon Guidance Assays in Three-Dimensional Culture
Terheyden-Keighley, D., Brand‐Saberi, B., & Theiß, C. (2016) · Journal of Neurology and Experimental Neuroscience · doi:10.17756/jnen.2016-015
“We hope that their implementation will aid the discovery of new neurotrophic factors, or identify neurotrophic effects in proteins previously thought unrelated to nervous system development, such as VEGF [22].”
BackgroundMiguel, V. T. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2019.tde-08082019-100009
Combining tissue engineering and gene delivery to enhance peripheral nerve regeneration
Busuttil, F. (2019) · UCL Discovery (University College London)
Inflammation and accumulating risk for developing psychiatric disorders
Money, K. M. (2016)
VEGF: A Key Player not Only in Macular Degeneration. A Review
Slíva, J. (2020) · Czech and Slovak Ophthalmology · doi:10.31348/2020/11
Liu, C. S. (2020) · TSpace (University of Toronto)
Schira‐Heinen, J. (2011) · Univ. Duesseldorf: Duesseldorfer Dokumenten- und Publikationsserver
(2005) · Kluwer Academic Publishers eBooks · doi:10.1007/0-306-48197-9_10
Oxygen Sensing and Hypoxia Signaling
(2005) · Kluwer Academic Publishers eBooks · doi:10.1007/0-306-48197-9_3
(2004) · Elsevier eBooks · doi:10.1016/b978-0-443-06711-2.50005-6
Response: Letter to the Editor
Haapaniemi, T., & Dahlin, L. (2003) · Journal of the Peripheral Nervous System · doi:10.1046/j.1529-8027.2003.03008.x
Karakulova, Y., & Филимонова, Т. А. (2022) · Biomarkers in disease · doi:10.1007/978-3-031-08014-2_60
Pak, S.-O., Ryu, J.-S., & Ro, H.-G. (2023) · International Journal of Clinical and Experimental Physiology · doi:10.5530/ijcep.2022.9.4.36
(2025) · Elsevier eBooks · doi:10.1016/b978-0-443-22065-4.00020-8
Epigenetic regulation of BDNF-TRKB signaling in the pathophysiology and treatment of mood disorders
Boulle, F. (2013) · theses.fr (ABES) · doi:10.70675/7796cc83z9f91z48c6zadb1zb6a90897b5d5
“A role in the development of dendrites and axons has also been described for VEGF (Khaibullina et al., 2004; Licht et al., 2010; Rosenstein et al., 2003; Sondell et al., 1999).”
BackgroundSchenkelaars, Q. (2015) · theses.fr (ABES) · doi:10.70675/678ad9b4z0094z499dzb772z9ec414b0d23e
Volpe, G., Bonanata, M., Peyla, A., Ruscitti, L., Eggarter, V., Pache, M., Paris, A., Menghini, M., & Grimaldi, G. (2026) · Ophthalmology and Therapy · doi:10.1007/s40123-026-01431-z
Predicting taxane-induced peripheral neuropathy by nailfold capillaroscopy: The CAPNEU pilot study
Alkan, A., Ersoy, M., Cenikli, U., Tarhan, E. F., & Tanrıverdi, Ö. (2026) · Supportive Care in Cancer · doi:10.1007/s00520-026-11043-9
Li, X., Cao, R., Wang, C., Chen, Z., Zhang, J., Li, Q., & Ma, X. (2026) · Orthopaedic Surgery · doi:10.1111/os.70393
Jiang, J., Safa, D., Knoedler, S. A., Altammar, J., Falkner, F., Hanschen, M., Kükrek, H., Dornseifer, U., Schilling, A. F., Machens, H.-G., et al. (2026) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2026.1901884
“VEGF-A, beyond its angiogenic role, exerts direct neurotrophic effects by enhancing neuronal survival and axonal outgrowth, thereby contributing to neurite elongation and structural stabilization during nerve regeneration (Sondell et al., 1999; Jin et al., 2006).”
Huang, L., Sun, T., Zhao, Y., Wu, Z., Sun, J., Li, M., Huo, Q., Ou, Y., Liang, Q., Ling, C., et al. (2026) · MedComm · doi:10.1002/mco2.71019
Vascular Endothelial Growth Factor: A Key Regulator of Physiologic Angiogenesis
Ferrara, N. (2001) · Birkhäuser Boston eBooks · doi:10.1007/978-1-4612-0213-4_8
Масгутов, Р. Ф., Salafutdinov, I. I., Bogov, A. A., Трофимова, А. А., Ханнанова, И. Г., Муллин, Р. И., Islamov, R. R., Челышев, Ю. А., & Rizvanov, A. A. (2011) · Genes and Cells
Flk-1 signalling during ES cell differentiation
McRae, L. A. (2007) · The University of Bath Online Publications Store (The University of Bath)
Apoptosis and Neurodegeneration in Diabetes: Lessons from the Retina
Barber, A. J., & Nakamura, M. (2002) · Springer eBooks · doi:10.1007/978-94-010-0614-9_4
Metadata
- Authors
- Sondell, M., Lundborg, G., & Kanje, M.
- Affiliations
- Lund University (SE)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-07-15
- Volume
- 19
- Issue
- 14
- Pages
- 5731-5740
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6783109
- OpenAlex
- W1962154683
- Cited by
- 750
- References
- 44
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 8 · 2023: 11 · 2022: 16 · 2021: 19 · 2020: 26 · 2019: 25 · 2018: 26 · 2017: 28 · 2016: 33 · 2015: 22 · 2014: 44 · 2013: 42 · 2012: 37
- FWCI
- 8.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- vascular endothelial growth factor, VEGF165, neurotrophic activity, axon growth, Schwann cell proliferation, satellite cells, superior cervical ganglion, dorsal root ganglia, MEK, PD98059, K252a, axon regeneration, peripheral nervous system, small-diameter neurons, cell survival
- MeSH terms
- Animals, Axons, Carbazoles, Cell Survival, Cells, Cultured, Enzyme Inhibitors, Flavonoids, Ganglia, Spinal, Humans, Lymphokines, Male, Mice, Inbred Strains, Nerve Growth Factors, Recombinant Proteins, Schwann Cells, Time Factors, Endothelial Growth Factors, Superior Cervical Ganglion, Indole Alkaloids, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Protein Kinase Inhibitors, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
