| Project/Area Number |
23390023
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokushima Bunri University |
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Principal Investigator |
IWATA Makoto 徳島文理大学, 薬学部, 教授 (50160122)
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| Co-Investigator(Kenkyū-buntansha) |
SONG Si-young 徳島文理大学, 神経科学研究所, 教授 (00399693)
KADOWAKI Norimitsu 京都大学, 大学院・医学系研究科, 准教授 (60324620)
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| Co-Investigator(Renkei-kenkyūsha) |
OHOKA Yoshiharu 徳島文理大学, 香川薬学部, 准教授 (60303971)
TAKEUCHI Hajime 徳島文理大学, 香川薬学部, 准教授 (00421298)
NAKATSUMA Aya 徳島文理大学, 香川薬学部, 助教 (30446075)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2011: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | 免疫学 / ビタミンA / レチノイン酸 / 樹状細胞 / T細胞 / DNAメチル化 / エピジェネティック / RALDH2 / 腸管 / Sp1 / 免疫寛容 |
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| Research Abstract |
Retinoic acid (RA)-producing dendritic cells (DC) are present in the gut-related tissue, and play important roles in the gut immunity. ALDH1A2 is the key enzyme for producing RA in these DC. The Aldh1a2 promoter region was GC-rich, and contained an Sp1-binding site and an RA response element (RARE) half-site near the TATA box. Among various animal species, the sequences of this region were well conserved. Sp1 and the RA receptor (RAR)/retinoid X receptor (RXR) heterodimer mutually enhanced their binding to these sites and cooperatively enhanced the promoter activity in the presence of RA. Accordingly, RA is an essential co-factor for inducing ALDH1A2 expression in DC. DNA methylation in the Aldh1a2 promoter region inhibited its activation. However, in normal DC subsets and other immune cells, the epigenetic regulation by Sp1 or histone acetylation but not DNA methylation appeared to participate in the regulation of RALDH2 gene expression.
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