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

doi:10.1016/j.brainresbull.2008.02.031

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

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

38 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 language	English
Pages (from-to)	368-375
Number of pages	8
Journal	Brain Research Bulletin
Volume	76
Issue number	4
DOIs	https://doi.org/10.1016/j.brainresbull.2008.02.031
Publication status	Published - 2008 Jul 1

Bibliographical note

Funding 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).

Keywords

Erk1/2
MMP-9
PAR1
Rat primary astrocytes
Thrombin

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/j.brainresbull.2008.02.031

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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

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

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.",

keywords = "Erk1/2, MMP-9, PAR1, Rat primary astrocytes, Thrombin",

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

note = "Funding 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).",

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AU - Choi, Min Sik

AU - Kim, Young Eun

AU - Lee, Woo Jong

AU - Choi, Ji Woong

AU - Park, Gyu Hwan

AU - Kim, Sun Don

AU - Jeon, Se Jin

AU - Go, Hyo Sang

AU - Shin, Sun Mi

AU - Kim, Won Ki

AU - Shin, Chan Young

AU - Ko, Kwang Ho

N1 - Funding 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).

PY - 2008/7/1

Y1 - 2008/7/1

N2 - 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.

AB - 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.

KW - Erk1/2

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KW - PAR1

KW - Rat primary astrocytes

KW - Thrombin

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AN - SCOPUS:44149086369

SN - 0361-9230

VL - 76

SP - 368

EP - 375

JO - Brain Research Bulletin

JF - Brain Research Bulletin

IS - 4

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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