| Project/Area Number |
04558024
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
物質生物化学
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| Research Institution | Kanazawa University |
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Principal Investigator |
YAMAMOTO Hiroshi Kanazawa Univ.Sch.of Med., Dep.of Biochem. Prfessor and Chairman, 医学部, 教授 (00115198)
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| Co-Investigator(Kenkyū-buntansha) |
KANEKO Tsuguhisa Kanazawa Univ.Sch.of Med., Dep.of Biochem.Instructor, 医学部, 助手 (60019560)
HOSONO Ryuji Kanazawa Univ.Sch.of Med., Dep.of Biochem.Assistant Professor, 医学部, 講師 (40019617)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥17,600,000 (Direct Cost: ¥17,600,000)
Fiscal Year 1994: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1993: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1992: ¥10,200,000 (Direct Cost: ¥10,200,000)
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| Keywords | blood brain barrier / vascular endothelial cells / pericytes / astroglial cells / advanced glycation endproducts / diabetic microangiopathy / aldosterone / vascular endothelial growth factor / トランス分化 / 血管平滑筋細胞 / ミネラルコルチコイドレセプター / vascular endothelial growth factor(VEGF) / 内皮細胞 / グリア細胞 / 多価陽イオン化アルブミン / 還元標識 / 拡散チェインバー / 血管周皮細胞 |
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| Research Abstract |
(1) In the present study, we have established an in vitro model of "blood brain barrier". With vascular endothelial cell, pericyte and astroglial cell co-culture systems, the barrier as well as transport activities selective to brain vessels were reconstituted, which passed polycationic albumin but excluded native albumin or inulin in the physiological polarity. This model would seem to be useful in screeeing substances that could act on the central nervous system and in evaluating their delivery into the brain. The present study has also demonstrated that astroglial cells are capable of "transdifferentiating "non-brain-type endothelial cells into brain-type ones : human umbilical vein endothelial cells co-cultured with astroglial cells did express the brain endothelium-specific genes, including those for gamma-transglutamyl transpeptidase, transferrin receptor and P-glycoprotein, and aquired the anti-inulin barrier propert. Although we failed to develop brain-specific transport vectors, new discoveries (2) that advanced glycation endproducts selectively injure pericytes through interactions with their cell-surface receptors, (3) that endothelial cells and vascular smooth muscle cells possess the devices both for synthesizing and for responding to aldosterone, a steroid implicated in the regulation of blood pressure, and (4) that hypoxia-induced proliferation of vascular cells in mediated by autocrine vascular endothelial growth factor, were made during the course of this study, and we have thus proposed novel mechanisms underlying the development and progression of various human vascular disorders including diabetic microangiopathy, hypertension and angiogenesis.
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