| Project/Area Number |
26860078
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
Akihiro Watari 大阪大学, 薬学研究科(研究院), 助教 (80452465)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 上皮バリア機能制御 / 炎症性腸疾患治療法 / クローディン発現 / タイトジャンクション / 炎症性腸疾患 / クローディン / 上皮バリア / daunorubicin / rebeccamycin |
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| Outline of Final Research Achievements |
In this study, we identified daunorubicin and rebecamycin as novel claudin modulators, which can enhance tight junction (TJ) barrier function in intestinal cells. Daunorubicin and rebeccamycin stimulate ATM and ATR kinases in the nucleus, resulting in activation of the downstream molecule, Chk1. Activated Chk1 increases claudin-5 expression, and the product of claudin-5 transitions to TJ following enhanced TJ-barrier. Furthermore, we constituted claudin-2 reporter system, and identified novel claudin-2 modulators from chemical library. In the future, we will investigate therapeutic effect of multiple claudin modulators for an inflammatory bowel disease.
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