| Project/Area Number |
24390089
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
KOJIMA Takashi 札幌医科大学, 医学部, 教授 (30260764)
TANAKA Satoshi 札幌医科大学, 医学部, 講師 (30374250)
MURATA Masaki 札幌医科大学, 医学部, 講師 (10404592)
TAKASAWA Akira 札幌医科大学, 医学部, 助教 (00593021)
GO Mitsuru 札幌医科大学, 医学部, 講師 (80448604)
IMAMURA Masafumi 札幌医科大学, 医学部, 助教 (00404608)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | タイト結合 / 膵癌 / 肝線維症 / 緑膿菌 / クローディン / PKC / EMT |
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| Outline of Final Research Achievements |
The tight junction, intercellular junction, works as barriers between outside and inside of the body, meaning one of drug delivery paths. In polarized cells, the junction performs to maintain cellular polarity. In this project showed the following points. Elastase of Pseudomonas aeruginosa causes transient disruption of tight junctions and downregulation of PAR-2 in human nasal epithelial cells. Tight junction protein claudin-4 is receptor of Clostridium perfringens enterotoxin（CPE） C-CPE recombinant peptides lacking cytotoxic activity also decreased the barrier function. These reversible changes of barrier function are highly applicable for developing new drug delivery techniques. Claudin-4 was up-regulated in human prostate cancer. Cytotoxic effect of CPE depended on the expression level of claudin-4 protein. In normal human prostate epithelial cells, however, the cytotoxic effect was barely detected. These findings suggest that CLDN-4 is a promising target of cancer therapy.
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