title: Breviscapine inhibits high glucose-induced proliferation and migration of cultured vascular smooth muscle cells of rats via suppressing the ERK1/2 MAPK signaling pathway.
abstract: OBJECTIVE
  To investigate the influences of breviscapine, a flavonoid extracted from Erigeron breviscapus, on the proliferation and migration of vascular smooth muscle cells (VSMCs) cultured in a high glucose medium and the underlying mechanisms.
  
  
  METHODS
  VSMCs were isolated from thoracic aortas of male Sprague-Dawley rats and cultured in vitro. Cell proliferation was evaluated using Counting Kit-8 cell viability assay. Cell migration was evaluated using transwell migration assay and in vitro scratch assay. The expression and activity of protein kinase C-β2 (PKC-β2), extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38), and JNK mitogen-activated protein kinase (JNK) were measured with Western blotting.
  
  
  RESULTS
  Exposure of VSMCs to a high glucose (25 mmol/L) medium significantly increased the proliferation and migration potential as compared to the control group. Pretreatment with breviscapine (65 μmol/L and 108 μmol/L) attenuated high glucose-enhanced proliferation and migration of VSMCs. Exposure of VSMCs to the high glucose medium activated both the PKC-β2 and ERK1/2 MAPK, but not the p38 and JNK MAPK. Pretreatment with breviscapine (65 μmol/L and 108 μmol/L) blocked high glucose-induced increase of the ERK1/2 activity, but not that of the PKC-β2 activity.
  
  
  CONCLUSIONS
  Our study demonstrated that breviscapine ameliorates high glucose-induced proliferation and migration of VSMCs via inhibiting ERK1/2 MAPK signaling.
authors.affiliation: The Department of Cardiology, Biomedical Research Therapy Center, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Meng
authors.initials: M
authors.lastname: He
authors.forename: Zhi-min
authors.initials: ZM
authors.lastname: Xue
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Bin-quan
authors.initials: BQ
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism; D064546:Protein Kinase C beta; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D005419:Flavonoids; D047428:Protein Kinase Inhibitors; C061097:breviscapine; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D048031:JNK Mitogen-Activated Protein Kinases; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose