Investigation of the expression mechanism of retinoic acid-generating enzyme, RALDH2, which plays key roles in gut immunity
| Project/Area Number |
24590106
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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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 |
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| Co-Investigator(Renkei-kenkyūsha) |
NAKATSUMA Aya (YOKOTA Aya) 徳島文理大学, 香川薬学部, 助教 (30446075)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 腸管免疫 / レチノイン酸 / GM-CSF / Sp1 / RAR / DNAメチル化 / RALDH2 / 樹状細胞 / エピジェネティック / メチル化 / レチノイン酸受容体 / ビタミンA / CpGアイランド |
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| Outline of Final Research Achievements |
GM-CSF potently induces RALDH2 expression in DCs in an RA-dependent manner, and RA alone weakly induces the expression. In this study, we show that GM-CSF-induced activation of the transcription factor Sp1 and RA-dependent signaling via the RAR/RXR complex contribute to Aldh1a2 expression. The RAR antagonist LE540 and the Sp1 inhibitor mithramycin A inhibited GM-CSF-induced Aldh1a2 expression in Flt3L-generated BM-DCs. Sp1 and the RARα/RXRα complex bound to GC-rich Sp1-binding sites and an RARE half-site, respectively, near the TATA box in the mouse Aldh1a2 promoter. The DNA sequences around these sites were highly conserved among different species. In the presence of RA, ectopic expression of RARα/RXRα and Sp1 synergistically enhanced Aldh1a2 promoter-reporter activity. These results suggest that GM-CSF/RA-induced RALDH2 expression in DCs requires cooperative binding of Sp1 and the RAR/RXR complex to the Aldh1a2 promoter.
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Report
(4 results)
Research Products
(9 results)
