期刊
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
卷 33, 期 3, 页码 661-669出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2014.1618
关键词
blood-brain barrier; Rho kinase; matrix metalloproteinase-9; urokinase-type plasminogen activator; lysophosphatidic acid
资金
- National Natural Science Foundation of China [81300984]
- Natural Science Foundation of Huber Province of China [2010CHB02001]
- Innovation Seed Fund of Wuhan University School of Medicine
Lysophosphatidic acid (LPA) the simplest of the water-soluble phospholipids, is produced by activated platelets, macrophage and endothelial cells. It also evokes various biological responses. When LPA concentrations reach high levels, brain injury, including stroke and intracerebral hemorrhage (ICH), occurs. Previous studies have shown that LPA is crucial in increasing blood-brain barrier (BBB) permeability, and the Rho/Rho kinase (ROCK) signaling pathway is involved in the regulation of endothelial permeability. However, the exact mechanism by which the Rho/ROCK pathway mediates BBB disruption induced by LPA remains to be determined. In the present study, we observed that LPA induced the increase of BBB permeability in the right striatum after 10 mu l LPA (100 mu M) was injected into the ipsilateral caudate nucleus of rats. The ROCK was involved in the expression of proteolytic enzymes, matrix metalloproteinase (MMP)-9 and urokinase-type plasminogen activator (uPA), leading to LPA-induced BBB disruption. ROCK inhibitor (Y27632) markedly inhibited the expression of proteolytic enzymes induced by LPA as well as the BBB disruption after it was co-injected with LPA. Thus, results of the present study suggest that LPA increases BBB permeability, which may be due to the Rho/ROCK signaling pathway and the subsequent production of proteolytic enzymes MMP-9 and uPA.
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