Activation of protease-activated receptor1 mediates induction of matrix metalloproteinase-9 by thrombin in rat primary astrocytes
- Authors
- Choi, Min Sik; Kim, Young Eun; Lee, Woo Jong; Choi, Ji Woong; Park, Gyu Hwan; Kim, Sun Don; Jeon, Se Jin; Go, Hyo Sang; Shin, Sun Mi; Kim, Won-Ki; Shin, Chan Young; Ko, Kwang Ho
- Issue Date
- 1-7월-2008
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- thrombin; MMP-9; PAR1; rat primary astrocytes; Erk1/2
- Citation
- BRAIN RESEARCH BULLETIN, v.76, no.4, pp.368 - 375
- Indexed
- SCIE
SCOPUS
- Journal Title
- BRAIN RESEARCH BULLETIN
- Volume
- 76
- Number
- 4
- Start Page
- 368
- End Page
- 375
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/123047
- DOI
- 10.1016/j.brainresbull.2008.02.031
- ISSN
- 0361-9230
- 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 mu M) 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 PARI 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. (c) 2008 Elsevier Inc. All rights reserved.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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