2005 Fiscal Year Final Research Report Summary
ROLE OF ENDOTHELIAL CELL, PERICYTE, AND ASTROCYTE ON BASEMENT MEMBRANE METABOLISM IN BLOOD-TISSUE BARRIER
| Project/Area Number |
16590120
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Kyoritsu University of Pharmacy |
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Principal Investigator |
NAKASHIMA Emi KYORITSU UNIVERSITY OF PHARMACY, DEPARTMENT OF PHARMACEUTICS, PROFESSOR, 薬学部, 教授 (90115254)
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| Co-Investigator(Kenkyū-buntansha) |
SAI Yoshimichi KYORITSU UNIVERSITY OF PHARMACY, DEPARTMENT OF PHARMACEUTICS, ASSOCIATE PROFESSOR, 薬学部, 助教授 (40262589)
KOSE Noriko KYORITSU UNIVERSITY OF PHARMACY, DEPARTMENT OF PHARMACEUTICS, ASSISTANT PROFESSOR, 薬学部, 助手 (60348612)
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| Project Period (FY) |
2004 – 2005
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| Keywords | blood-brain barrier / basement membrane / endothelial cell / pericyte / astrocyte / endothelial progenitor cell / smooth muscle cell / conditionally immortalized cell line |
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| Research Abstract |
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 inter-relationships in formation or maintenance of basement membrane are poorly understood. Previously, we established the conditionally immortalized cell lines of brain capillary pericyte (TR-PCT), bone marrow endothelial progenitor cell derived cell (TR-BME) from the transgenic rats with a temperature sensitivity SV40 T antigene gene. It was found that the mRNA level of α-smooth muscle actin in a brain capillary pericyte cell line TR-PCT1 was increased by treatment with TGF-β1. TR-PCTs retained biological activity of the calcification to matrix by the b-glycerophosphate.
In this study, the 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 analysis. The effects of TGF-β1 on expression of basement membrane-related genes in these cell lines were also examined. In order to identify the role of endothelial progenitor cells on barrier function, we compared the specific genes by means of subtractive hybridization between TR-BBB and TR-BME cells.
Collagen type IV is the main constituent, and produced mainly by astrocyte. TR-PCT produce fibronectine, about 5 times higher than that of endothelial cell. TR-PCT showed high expressions of MMP-9 and tPA, the decomposition component of basement membrane. Thus, we showed that pericyte is highly active and may be a key cell which control the regulation of basement membrane. TR-BME cells have higher levels of smooth muscle cell(SMC) markers compared with mature endothelial cell, and can differentiate into contractile- or synthetic-type SMC.
These results suggest that pericytes and progenitor cells may be key cells in the maintenance of basement membrane and its function.
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