Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling

Yi Chang, Yih Huei Uen, Chang Chih Chen, Song-Chow Lin, Shiao Yun Tseng, Yi Hsuan Wang, Joen Rong Sheu, Cheng Ying Hsieh

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9 Citations (Scopus)

Abstract

Aim: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.Conclusion: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.

Original languageEnglish
Pages (from-to)1337-1344
Number of pages8
JournalActa Pharmacologica Sinica
Volume32
Issue number11
DOIs
Publication statusPublished - Nov 2011

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Keywords

  • cell cycle
  • JNK1/2
  • p27
  • PDGF-BB
  • vascular smooth muscle cells

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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