| Co-Investigator(Kenkyū-buntansha) |
IIZASA Hisashi KYORITSU UNIVERSITY OF PHARMACY, DEPARTMENT OF PHARMACY, ASSISTANT PROFESSOR, 薬学部, 助手 (80306662)
ISAWA Minae KYORITSU UNIVERSITY OF PHARMACY, DEPARTMENT OF PHARMACY, ASSISTANT PROFESSOR, 薬学部, 助手 (10338006)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
1.Augmented Expression of the Tight Junction Protein Occludin in Brain Endothelial Cell Line TR-BBB by Rat Angiopoietin-1 Expressed in Baculovirus-Infected Sf Plus Insect:
The blood-brain barrier(BBB), which has extremely low drug permeability, is composed of rain endothelial cells linked together by tight junctions(TJ). Occludin plays a key role in TJ formation and BBB maturation. However, the physiologic regulator of the expression of occludin in the BBB is not known. We describe the molecular cloning of rat ang-1, and its expression in baculovirus-infected Sf plus cells. The recombinant rat ang-1 induced expression of occludin in the brain capillary cell line TR-BBB in vitro.
2.Rat Brain Pericyte Cell Lines Expressing B2-Adrenergic Receptor, Angiotensin II Receptor type 1A, Klotho, and CXCR4 mRNAs Despite Having Endothelial Cell Markers:
Perycites are an integral component of blood capillaries, but their involvement in a variety of conditions and disease is poorly understood. We establ
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ished TR-PCT cell lines and found that TR-PCTs express B2-adrenergic receptor, angiotensin II receptor type 1A, klotho, and CXCR4. We showed that established cell lines are pluripotent, and should be useful for analysis of the reactivity and biological roles of pericytes.
3.A Perycite-derived Angiopoietin-1 induces Occluding Gene Expression in Brain Capillary Endothelial Cells:
In order to identify molecules, which regulate occluding expression, derived from astrocytes and pericytes that ensheathe brain microvessels, we established the in vitro model by using TR-BBB and TR-PCT. Transfilter co-culture with TR-PCT increased occludin mRNA in TR-BBB cells. The increased occludin up-regulation was significantly inhibited by an ang-1-neutralizing antibody. Immunoprecipitation and western blot analyses confirmed that multimeric ang-1 is secreted from TR-PCT, and induces occludin mRNA, acting through tyrosine phosphorylation of Tie-2 in BBB cells. Thus, we revealed that the pericyte-derived multimeric ang-1/Tie-2 pathway induces occludin expression. Less
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