Abstract
Under conditions associated with local and systemic inflammation, mesangial cells and invading immune cells are likely to be responsible for the release of large amounts of nitric oxide (NO) in the glomerulus. To further define the mechanisms of NO action in the glomerulus, we attempted to identify genes which are regulated by NO in rat glomerular mesangial cells. We identified vascular endothelial growth factor (VEGF) and its receptor fms-like tyrosine kinase (FLT-1) to be under the regulatory control of exogenously applied NO in these cells. Using S-nitroso-glutathione (GSNO) as an NO-donating agent, VEGF expression was strongly induced, whereas expression of its FLT-1 receptor simultaneously decreased. Expressional regulation of VEGF and FLT-1 mRNA was transient and occurred rapidly within 1-3 h after GSNO treatment. Expression of a second VEGF-specific receptor, fetal liver kinase-1 (FLK-1/KDR), could not be detected. The inflammatory cytokine interleukin-1beta mediated a moderate increase in VEGF expression after 24 h and had no influence on FLT-1 expression. In contrast, platelet-derived growth factor-BB and basic fibroblast growth factor had no effect on VEGF expression, but strongly induced FLT-1 mRNA levels. Obviously, there is a differential regulation of VEGF and its receptor FLT-1 by NO, cytokines and growth factors in rat mesangial cells.
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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Cytokines / physiology
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DNA Primers
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Endothelial Growth Factors / genetics
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Endothelial Growth Factors / metabolism*
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Enzyme Activation
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Glomerular Mesangium / cytology
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Glomerular Mesangium / metabolism*
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Glutathione / analogs & derivatives
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Glutathione / pharmacology
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Guanylate Cyclase / metabolism
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Inflammation Mediators
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Lymphokines / genetics
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Lymphokines / metabolism*
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Nitric Oxide / physiology*
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Nitric Oxide Donors / pharmacology
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Nitroso Compounds / pharmacology
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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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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S-Nitrosoglutathione
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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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Cytokines
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DNA Primers
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Endothelial Growth Factors
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Inflammation Mediators
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Lymphokines
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Nitric Oxide Donors
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Nitroso Compounds
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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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Nitric Oxide
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S-Nitrosoglutathione
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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
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Guanylate Cyclase
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Glutathione