title: Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling.
abstract: OBJECTIVE
  To examine the inhibitory actions of the immunoregulator platonin against proliferation of rat vascular smooth muscle cells (VSMCs).
  
  
  METHODS
  VSMCs were prepared from the thoracic aortas of male Wistar rats. Cell proliferation was examined using MTT assays. Cell cycles were analyzed using flow cytometry. c-Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, AKT, and c-Jun phosphorylation or p27 expression were detected using immunoblotting.
  
  
  RESULTS
  Pretreatment with platonin (1-5 μmol/L) significantly suppressed VSMC proliferation stimulated by PDGF-BB (10 ng/mL) or 10% fetal bovine serum (FBS), and arrested cell cycle progression in the S and G(2)/M phases. The same concentrations of platonin significantly inhibited the phosphorylation of JNK1/2 but not ERK1/2 or AKT in VSMCs stimulated by PDGF-BB. Furthermore, platonin also attenuated c-Jun phosphorylation and markedly reversed the down-regulation of p27 expression after PDGF-BB stimulation.
  
  
  CONCLUSIONS
  Platonin inhibited VSMC proliferation, possibly via inhibiting phosphorylation of JNK1/2 and c-Jun, and reversal of p27 down-regulation, thereby leading to cell cycle arrest at the S and G(2)/M phases. Thus, platonin may represent a novel approach for lowering the risk of abnormal VSMC proliferation and related vascular diseases.
authors: Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors: Yi
authors: Y
authors: Chang
authors: Yih-Huei
authors: YH
authors: Uen
authors: Chang-Chih
authors: CC
authors: Chen
authors: Song-Chow
authors: SC
authors: Lin
authors: Shiao-Yun
authors: SY
authors: Tseng
authors: Yi-Hsuan
authors: YH
authors: Wang
authors: Joen-Rong
authors: JR
authors: Sheu
authors: Cheng-Ying
authors: CY
authors: Hsieh
mesh_terms: D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D007155:Immunologic Factors; D018809:Proliferating Cell Nuclear Antigen; D020574:Proto-Oncogene Proteins c-sis; D013844:Thiazoles; C413374:p27 antigen; C032149:platonin; D000077214:Becaplermin; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3