期刊
DRUG METABOLISM AND PHARMACOKINETICS
卷 22, 期 4, 页码 255-266出版社
JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.2133/dmpk.22.255
关键词
brain pericyte; brain endothelial cell; astrocyte; transforming growth factor beta 1; basement membrane
The basement membrane at the blood-brain barrier (BBB) plays important roles in maintaining the structure and function of capillary vessels. The BBB is constructed from endothelial cells, astrocytes and pericytes, but their interactions in the formation or maintenance of basement membrane have not been established. Transforming growth factor-beta 1 (TGF-beta 1) is known to increase fibronectin in brain capillary basement membrane with deposition of beta-amyloid. We previously reported that the mRNA level of a-smooth muscle actin in a brain capillary pericyte cell line TR-PCT1 was increased by treatment with TGF-beta 1. In this study, expression of mRNAs encoding basement membrane-related molecules in TR-PCT1, a rat endothelial cell line TR-BBB13, and a type 2 astrocyte cell line TR-AST4 was evaluated by RT-PCR. The effects of TGF-beta 1 on expression of basement membrane-related genes in these cell lines were also examined. Fibronectin, MMP-9, tPA, TIMP-1, and PAI-1 in TR-PCT1 were higher than in TR-BBB13 and TR-AST4. In TR-PCT1 treated with TGF-beta 1, collagen type IV, PAI-1, and MMP-9 were increased, and TIMP-2 was reduced. The change in PAI-1 mRNA was faster than those in MMP-9, TIMP-2, collagen type IV mRNAs. These results suggest that pericytes may be key cells in the maintenance of the basement membrane at the BBB.
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