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.
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“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]
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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).”
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Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,526
Vascular Endothelial Growth Factor: Basic Science and Clinical Progress
Ferrara, N. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0027 · Cited by 3,788
Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo
Jin, K., Zhu, Y., Sun, Y., Mao, X. O., Xie, L., & Greenberg, D. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182296499 · Cited by 1,507
VEGF enhances angiogenesis and promotes blood–brain barrier leakage in the ischemic brain
Zhang, Z. G., Zhang, L., Jiang, Q., Zhang, R., Davies, K., Powers, C., Bruggen, N. V., & Chopp, M. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9369 · Cited by 1,296
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
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