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.
|Number of pages||8|
|Journal||Brain Research Bulletin|
|Publication status||Published - 2008 Jul 1|
Bibliographical noteFunding Information:
This research was supported by a grant (M103KV010025-06K2201-02510) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, the Republic of Korea, and by the Korea Research Foundation Grant (KRF-2002-E060601-ES0011) funded by the Korean Government (MOEHRD).
- Rat primary astrocytes
ASJC Scopus subject areas