title: 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.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To elucidate the mechanism how HGF and its receptor c-Met reduces angiotensin II (Ang II)-induced inflammation.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These data suggest that the HGF/c-Met system might regulate extrinsic factor signaling that maintains the homeostasis of organs.
authors.affiliation: Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Yamada-oka, Suita, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sanada
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Taniyama
authors.forename: Kazuma
authors.initials: K
authors.lastname: Iekushi
authors.forename: Junya
authors.initials: J
authors.lastname: Azuma
authors.forename: Keita
authors.initials: K
authors.lastname: Okayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kusunoki
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Koibuchi
authors.forename: Takefumi
authors.initials: T
authors.lastname: Doi
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D054875:Ubiquitination
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; C587883:HBEGF protein, human; C066855:HGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D017978:Receptors, Growth Factor; D000804:Angiotensin II; D017228:Hepatocyte Growth Factor; D013482:Superoxide Dismutase; C512478:EGFR protein, human; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D046988:Proteasome Endopeptidase Complex