Negative action of hepatocyte growth factor/c-Met system on angiotensin II signaling via ligand-dependent epithelial growth factor receptor degradation mechanism in vascular smooth muscle cells.
Neointimal hyperplasia contributes to atherosclerosis and restenosis after percutaneous coronary intervention. Vascular injury in each of these conditions results in the release of mitogenic growth factors and hormones that contribute to pathological vascular smooth muscle cell growth and inflammation. Hepatocyte growth factor (HGF) is known as an antiinflammatory growth factor, ... although it is downregulated in injured tissue. However, the precise mechanism how HGF reduces inflammation is unclear.To elucidate the mechanism how HGF and its receptor c-Met reduces angiotensin II (Ang II)-induced inflammation.HGF reduced Ang II-induced vascular smooth muscle cell growth and inflammation by controlling translocation of SHIP2 (Src homology domain 2-containing inositol 5'-phosphatase 2), which led to Ang II-dependent degradation of epithelial growth factor receptor. Moreover, the present study also revealed a preventive effect of HGF on atherosclerotic change in an Ang II infusion and cuff HGF transgenic mouse model.These data suggest that the HGF/c-Met system might regulate extrinsic factor signaling that maintains the homeostasis of organs.
Mesh Terms:
Angiotensin II, Angiotensin II Type 1 Receptor Blockers, Animals, Atherosclerosis, Cell Proliferation, Cells, Cultured, Hepatocyte Growth Factor, Humans, Hyperplasia, Inflammation, Intercellular Signaling Peptides and Proteins, Ligands, Mice, Mice, Inbred C57BL, Mice, Transgenic, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Phosphoric Monoester Hydrolases, Proteasome Endopeptidase Complex, Protein Processing, Post-Translational, Protein Transport, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-met, RNA Interference, Reactive Oxygen Species, Receptor, Epidermal Growth Factor, Receptors, Growth Factor, Signal Transduction, Superoxide Dismutase, Time Factors, Transfection, Ubiquitination
Angiotensin II, Angiotensin II Type 1 Receptor Blockers, Animals, Atherosclerosis, Cell Proliferation, Cells, Cultured, Hepatocyte Growth Factor, Humans, Hyperplasia, Inflammation, Intercellular Signaling Peptides and Proteins, Ligands, Mice, Mice, Inbred C57BL, Mice, Transgenic, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Phosphoric Monoester Hydrolases, Proteasome Endopeptidase Complex, Protein Processing, Post-Translational, Protein Transport, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-met, RNA Interference, Reactive Oxygen Species, Receptor, Epidermal Growth Factor, Receptors, Growth Factor, Signal Transduction, Superoxide Dismutase, Time Factors, Transfection, Ubiquitination
Circ. Res.
Date: Sep. 25, 2009
PubMed ID: 19713535
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