期刊
NEUROSCIENCE LETTERS
卷 599, 期 -, 页码 109-114出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2015.05.028
关键词
Brain pericytes; Blood-brain barrier; Thrombin; Protease-activated receptors; Matrix metalloproteinase-9; Intracerebral hemorrhage
资金
- Japan Society for the Promotion of Science [25460236, 26460113, 24790102, 26860177]
- Central Research Institute of Fukuoka University, Japan [141104, 136005]
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Takeda Science Foundation, Japan
- Grants-in-Aid for Scientific Research [26860177, 24790102, 25460236, 26460113] Funding Source: KAKEN
In the acute phase of intracerebral hemorrhage (ICH), hemorrhagic transformation and brain edema are associated with blood brain barrier (BBB) disruption. Elevated levels of thrombin, a coagulation factor, contribute to the development of brain edema during ICH through matrix metalloproteinase (MMP)-9 production. Thrombin directly induces a variety of cellular responses through its specific receptors known as protease-activated receptors (PARS). However, it remains unclear which cell types constituting the BBB mainly produce MMP-9 in response to thrombin. Here, we compared the MMP-9 release induced by thrombin using primary cultures of rat brain microvascular endothelial cells, astrocytes, and pericytes. Brain pericytes exhibited the highest levels of MMP-9 release due to thrombin stimulation among the BBB cells. The pattern of PAR mRNA expression in pericytes was characterized by high expression of PAR1 and moderate expression of PAR4. Heat-inactivated thrombin failed to stimulate pericytes to release MMP-9. A selective PAR1 inhibitor SCH79797 blocked the thrombin-induced MMP-9 release from pericytes. These findings suggest that both PAR1 and PAR4 mediate thrombin-induced MMP-9 release from pericytes. The present study raises the possibility that brain pericytes could play a pivotal role as a highly thrombin-induced and MMP-9-producing cell type at the BBB in brain damage including ICH. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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