| Project/Area Number |
18K15115
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Chiba Tomoki 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (00645830)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 長鎖非コードRNA / 炎症性サイトカイン / 炎症性腸疾患 / 転写制御 |
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| Outline of Final Research Achievements |
Recent advantages of transcriptome analyses revealed that non-coding RNAs, especially long non-coding (lnc) RNAs, are transcribed across genome and involved in various aspects of biological processes. I have identified a novel lncRNA that positively regulates inflammatory cytokine expression and named it LASC. LASC is required for the expression of inflammatory cytokines such as IL-6 and GM-CSF. Recruitment of transcription factor NF-kB was strongly reduced in LASC deficient cells, suggesting that LASC could regulate inflammatory cytokine expression at transcriptional level. LASC knockout mice are resistant to sepsis, but susceptible to inflammatory bowel disease. These results suggest that LASC is important for maintaining intestinal homeostasis through the regulation of inflammatory cytokine expression in mucosal cells.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトやマウスにおいて、タンパク質をコードしない非コードRNA（non-coding RNA）は20,000種類以上あると推定されている。その多くは機能を持たないRNAであると考えられているが、一部のRNAは生命機能に重要な役割を果たしている。新たに同定したLASCは炎症性サイトカインの発現に重要な長鎖非コードRNAであり、個体における炎症性疾患に重要な非コードRNAであることが示された。
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