| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Outline of Final Research Achievements |
Based on the previous findings, we studied molecular mechanisms by which 1-1) a protein crosslinking enzyme, transglutaminase 2 (TG2) promotes cancer angiogenesis and 1-2) co-culture with fungi induces nuclear TG2 activity in hepatic cells, and 2) screened a food-derived compounds that control the above clarified mechanisms. We found 1-1) TG2 inversely regulates the expression of an endogenous angiogenesis inhibitor, vasohibin 1, in lung endothelial cell cultures, animal models, and patients with lung carcinoma, 1-2) C. albicans and C. glabrata but not S. cerevisiae induces increased nuclear TG2 activity in hepatic cells via producing reactive oxygen species, and 2) phenosafranine inhibits nuclear transportation but not activity of TG2. These results suggest phenosafranine will be promising to suppress nuclear TG2-mediated pathogenesis such as cancer angiogenesis and hepatic injury, but not affect cytosolic TG2-mediated physiological role of TG2 such as promotion of tissue remodeling.
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