2002 Fiscal Year Final Research Report Summary
Regulation of the tight junction barrier by synthetic peptides: Towards the development of a new drug delivery method
| Project/Area Number |
13557013
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
FURUSE Mikio KYOTO UNIVERSITY, FACULTY OF MEDICINE ASSOCIATE PROFESSOR, 医学研究科, 助教授 (90281089)
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| Co-Investigator(Kenkyū-buntansha) |
KUBO Akiharu KYOTO UNIVERSITY, FACULTY OF MEDICINE ASSISTANT, 医学研究科, 助手 (70335256)
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| Project Period (FY) |
2001 – 2002
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| Keywords | claudin / occludin / tight junction / barrier / peptide / drug delivery / blood-brain barrier / ZO-1 |
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| Research Abstract |
The blood-brain barrier (BBB) is thought to protect the brain from various harmful materials circulating in the blood. On the other hand, BBB prevents many potential drugs from entering the central nervous system (CNS). Many researchers have therefore tried to loosen the BBB for therapeutic purposes in various CNS disorders, but limited information on the molecular basis for BBB has hampered these trials. To establishment of the BBB, well-developed tight junctions (TJs) between adjacent endothelial cells are indispensable, in addition to various transporters in their plasma membranes. Recently, claudin-5 was identified as a major TJ cell adhesion molecule in brain endothelial cells. Here we show that in claudin-5-deficient mice, BBB is loosened in a size-selective manner. In the brain of these mice, the morphology/development of blood vessels was not altered, and TJs consisting of claudin-12 remained in the endothelial cells. Tracer experiments and magnetic resonance imaging revealed that in the claudin-5-deficient brain, the BBB against small molecules (<800 Da), but not larger molecules, was selectively affected. These findings not only provide new insight into the basic molecular physiology of BBB but also improve drug delivery methods.
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Research Products
(15 results)
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[Publications] Miwa, N., Furuse, M., Tsukita, Sh., Niikawa, N., Nakamura, Y and Furukawa, Y,: "Involvement of claudin-1 in the beta-catenin/Tcf signaling pathway and its frequent upregulation in human colorectal cancers"Oncology Res.. 12. 469-476 (2001)
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[Publications] Itoh, M., Sasaki, H., Furuse, M., Ozaki, H., Kita, T., and Tsukita, Sh.: "Junctional adhesion molecule (JAM) binds to PAR-3: a possible mechanism for the recruitment of PAR-3 to tight junctions"J. Cell Biol.. 154. 491-497 (2001)
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[Publications] Furuse, M., Hata, M., Furuse, K., Yoshida, Y., Haratake, A., Sugitani, Y., Noda, T., Kubo, A. and Tsukita, Sh.: "Claudin-based tight junctions are crucial for the mammalian epidermal barrier: A lesson from claudin-1-deficient mice"J. Cell Biol.. 156. 1099-1111 (2002)
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[Publications] Morita, K., Furuse, M., Yoshida, Y., Itoh, M., Sasaki, H., Tsukita, Sh. and Miyachi, Y.: "Molecular architecture of tight junctions of periderm differs from that of the maculae occludentes of epidermis"J. Invest. Dermatol.. 118. 1073-1079 (2002)
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