Abstract
Vascular endothelial growth factor (VEGF) acts primarily as an endothelial cell mitogen via the "endothelial cell-specific" receptors VEGFR-1 (flt-1) and VEGFR-2 (flk-1/KDR). Only a few nonendothelial cells have been shown to possess functional VEGF receptors. We therefore examined the rat renal tubular epithelial cell line NRK52-E. NRK52-E expressed VEGFR-1 and VEGFR-2 mRNA and protein by RT-PCR, Northern blotting, Western blotting, immunofluorescence, and ligand binding. Serum-starved NRK52-E incubated with VEGF showed a significant increase in [(3)H]thymidine incorporation compared with control (2.3-fold at 1-10 ng/ml, P < 0. 05; 3.3-fold at 50-100 ng/ml, P < 0.01). VEGF also protected NRK52-E from hydrogen peroxide-induced apoptosis and necrosis compared with control (annexin-V-FITC-positive cells, 39 vs. 54%; viable cells, 50. 5 vs. 39.7%). Immunohistochemical staining using a variety of antibodies showed expression of both VEGF receptors in normal rat renal tubules in vivo. Because VEGF induced a proliferative and an antiapoptotic response in renal tubular epithelial cells, these data suggest that VEGF may act as a survival factor for renal tubular epithelium in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Blotting, Northern
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Blotting, Western
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Cell Division
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Cell Line
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Cell Survival / physiology
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DNA Primers / genetics
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Endothelial Growth Factors / physiology*
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Epithelial Cells / cytology
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Epithelial Cells / physiology
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Immunohistochemistry
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Kidney Tubules / cytology*
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Kidney Tubules / physiology*
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Lymphokines / physiology*
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Microscopy, Confocal
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptors, Growth Factor / genetics
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Receptors, Growth Factor / metabolism
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Receptors, Vascular Endothelial Growth Factor
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Reverse Transcriptase Polymerase Chain Reaction
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factors
Substances
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DNA Primers
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Endothelial Growth Factors
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Lymphokines
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Proto-Oncogene Proteins
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RNA, Messenger
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Receptors, Growth Factor
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Receptor Protein-Tyrosine Kinases
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Receptors, Vascular Endothelial Growth Factor
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Vascular Endothelial Growth Factor Receptor-1