Abstract
Angiotensin II (Ang II), a vasoactive peptide that is also considered a growth factor, has been implicated in both normal and diabetic cellular proliferation. We recently found that activation of janus kinase 2 (JAK2) is essential for the Ang II-induced proliferation of vascular smooth muscle cells (VSMCs) and that high glucose augments Ang II-induced proliferation of VSMCs by increasing signal transduction through activation of JAK2. Here, we demonstrate that S100B, a ligand for the receptor of advanced glycation end products (RAGEs), augmented both Ang II-induced tyrosine phosphorylation of JAK2 and cell proliferation in VSMCs in a receptor-dependent manner. We also found that S100B-RAGE interaction triggered intracellular generation of reactive oxygen species (ROS), VSMC proliferation, and JAK2 tyrosine phosphorylation via activation of phospholipase D (PLD)2. These results provide direct evidence for linkages between PLD2, ROS production, and S100B-RAGE-induced enhancement of Ang II-induced cell proliferation and activation of JAK2 in VSMCs.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Angiotensin II / pharmacology*
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Animals
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Antibodies / pharmacology
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Aorta / cytology
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Cell Division / drug effects
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Cells, Cultured
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DNA-Binding Proteins / metabolism
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Drug Synergism
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Electroporation
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Hydrogen Peroxide / metabolism
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Janus Kinase 2
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Ligands
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects*
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Muscle, Smooth, Vascular / enzymology
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NADPH Oxidases / metabolism
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Phospholipase D / antagonists & inhibitors
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Phospholipase D / metabolism*
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Phosphoproteins / antagonists & inhibitors
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Phosphoproteins / immunology
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Phosphorylation / drug effects
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Proteins*
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Rats
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Reactive Oxygen Species / metabolism
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Receptor for Advanced Glycation End Products
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Receptors, Immunologic / antagonists & inhibitors
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism*
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S100 Proteins / metabolism
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S100 Proteins / pharmacology*
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STAT1 Transcription Factor
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Trans-Activators / metabolism
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Tyrosine / metabolism
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Vasoconstrictor Agents / pharmacology*
Substances
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Antibodies
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DNA-Binding Proteins
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Ligands
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Phosphoproteins
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Proto-Oncogene Proteins
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Reactive Oxygen Species
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Receptor for Advanced Glycation End Products
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Receptors, Immunologic
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S100 Proteins
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S100A1 protein
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STAT1 Transcription Factor
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Trans-Activators
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Vasoconstrictor Agents
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Angiotensin II
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Tyrosine
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Hydrogen Peroxide
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NADPH Oxidases
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neutrophil cytosolic factor 1
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Protein-Tyrosine Kinases
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Jak2 protein, rat
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Janus Kinase 2
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phospholipase D2
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Phospholipase D