| Project/Area Number |
16K09753
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | The University of Tokushima |
|---|
Principal Investigator |
SAKAUE Hiroshi 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (60372645)
|
|---|
| Research Collaborator |
KURODA masashi
TSUTSUMI rie
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
|---|
| Keywords | 脂肪細胞 / 肥満 / メタボリックシンドローム / 転写因子 / IRF7 / ベージュ脂肪細胞 / UCP-1 / MCP-1 / 2型糖尿病 / 糖尿病 |
|---|
| Outline of Final Research Achievements |
Through the combination of DNA microarray and genomic data analysis to predict DNA binding motif, we have identified the transcription factor, Interferon Regulatory Factor 7 (IRF7) as a possible regulator of the genes related to adipocyte hypertrophy. To clarify the role of IRF7 in adipocytes, we found that enforced expression of IRF7 induced the transcription of Monocyte Chemoattractant Proteoin-1 (MCP-1), a key initial adipokine in chronic inflammation in obesity. CRISPR/Cas9 mediated-suppression of IRF7 leaded to significant reduction of MCP-1 mRNA. Luciferase assay and ChIP-PCR analysis shows that IRF7 transactivates MCP-1 gene. Taken together, our results suggest that IRF7 trans-activates MCP-1 mRNA in adipocyte, and might be involved in adipose tissue inflammation associated with obesity.
|
| Academic Significance and Societal Importance of the Research Achievements |
肥満形成とその病態発症機構における転写因子IRF7の役割が解明できうるとできたと考えられ、IRF7を分子標的とした新しい肥満・メタボリックシンドローム治療への意義を確立しえた。さらにTLR9-IRF7パスウエイを阻害する小分子化合物や薬剤の探索への基礎的基盤が確立した。TLR9-IRF7パスウエイを活性化するリガンド（DNAなど）を探索し、肥満モデルマウスに対して、受容体阻害薬の効果を検討することで、肥満とそれに伴う生活習慣病の治療に新たなアイデアが提供できたことからも、その社会的意義は大きい。
|
