| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Outline of Final Research Achievements |
The present research demonstrated that the co-transfected SRC-1 increased transcriptional activity of PPARγ and PAX8-PPARγ on the AQP7 promoter in the presence of ciglitizone. On the other hand, co-transfected PGC-1 strongly upregulated PAX8-PPARγ transcriptional activity on the AQP7 promoter even in the absence of ciglitizone. We confirmed that these transcriptional effects depend primarily on the presence of the PPARγ DNA binding domain (DBD), such that either mutation of the PPARγ DBD in PAX8-PPARγ, or mutation of the putative PPARγ response element, was sufficient to abolish PAX8-PPARγ-mediated regulation of the AQP7 promoter. We conclude that PAX8-PPARγ has strong ligand-independent activity on AQP7 transcription that may be mediated via its interaction with PGC-1α and that ligand-dependent activity may be mediated via SRC-1 recruitment.
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