Activation of protease-activated receptor1 mediates induction of matrix metalloproteinase-9 by thrombin in rat primary astrocytes

Min Sik Choi, Young Eun Kim, Woo Jong Lee, Ji Woong Choi, Gyu Hwan Park, Sun Don Kim, Se Jin Jeon, Hyo Sang Go, Sun Mi Shin, Won Ki Kim, Chan Young Shin, Kwang Ho Ko

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32 Citations (Scopus)

Abstract

Thrombin plays an important role in diverse neurological processes such as proliferation, cell migration, differentiation and neuroinflammation. In this study, we investigated the effect of thrombin on matrix metalloprotease-9 (MMP-9) expression in rat primary astrocytes. Thrombin (1-10 U/ml) induced a significant increase in MMP-9 activity as measured by gelatin zymography. Thrombin also increased MMP-9 mRNA expression. Among three isotypes of thrombin receptor, i.e. protease-activated receptor (PAR)-1, -3 and -4, PAR1 agonist (1-100 μM) but not PAR3 and PAR4 agonist induced MMP-9 expression. Inhibition of thrombin-induced MMP-9 production by SCH 79797 (10-50 nM), a selective PAR1 receptor antagonist, confirmed that PAR1 is a main receptor for thrombin-induced MMP-9 expression. In astrocytes, thrombin activated Erk1/2, and it was inhibited by PD98059. In this study, thrombin-induced MMP-9 expression was inhibited by PD98059. PAR1 agonist activated Erk1/2 and PD98059 inhibited PAR1 agonist-induced MMP-9 expression. MMP-9 promoter reporter assay confirmed the positive effect of ERK1/2 on MMP-9 expression. These results suggest that the activation of PAR1 mediates thrombin-induced MMP-9 expression through the regulation of Erk1/2.

Original languageEnglish
Pages (from-to)368-375
Number of pages8
JournalBrain Research Bulletin
Volume76
Issue number4
DOIs
Publication statusPublished - 2008 Jul 1

Keywords

  • Erk1/2
  • MMP-9
  • PAR1
  • Rat primary astrocytes
  • Thrombin

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Choi, M. S., Kim, Y. E., Lee, W. J., Choi, J. W., Park, G. H., Kim, S. D., Jeon, S. J., Go, H. S., Shin, S. M., Kim, W. K., Shin, C. Y., & Ko, K. H. (2008). Activation of protease-activated receptor1 mediates induction of matrix metalloproteinase-9 by thrombin in rat primary astrocytes. Brain Research Bulletin, 76(4), 368-375. https://doi.org/10.1016/j.brainresbull.2008.02.031