Development of inflammatory bowel disease treatment by restoration of intestinal epithelial barrier functions

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860078
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Osaka University
• Principal Investigator: Akihiro Watari 大阪大学, 薬学研究科(研究院), 助教 (80452465)
• Project Period (FY): 2014-04-01 – 2016-03-31
• 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

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.

Free Research Field

分子細胞生物学