2013 Fiscal Year Research-status Report
Effects of Runx1-associated lncRNA on asthma pathogenesis
| Project/Area Number |
25860374
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
SEO WOOSEOK 独立行政法人理化学研究所, 統合生命医科学研究センター, 国際特別研究員 (40574116)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | CD4T細胞 / Runx1転写因子 / long non-coding RNA / ヒト喘息疾患発症 |
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| Research Abstract |
Runx1 protein is a transcription factor which has critical functions in development. Deletion of Runx1 in mouse not only exhibit defected developmental processes, but also various autoimmune diseases, especially a human asthma-like pathology. Our laboratory showed that this pathology is caused by overexpression of IL-4, a cytokine essential for asthma pathogenesis, in the absence of Runx1. This observation prompted us to propose that Runx1 might actively function to control immune responses in addition to the well-established roles in development.
In search of molecular mechanisms by which Runx1 regulates immune responses, we discovered a novel lncRNA (long non-coding RNA) around Runx1 gene locus and found that this lncRNA (Runx1-lncRNA1) is expressed in helper T lymphocytes and specifically bind to Runx1 protein. Interestingly, siRNA (small interfering RNA)-mediated knockdown of Runx1-lncRNA1 from helper T lymphocytes in vitro resulted in phenotypes resembling deletion of Runx1 such as increases in IL-4 expression. Therefore, we hypothesize that Runx1-lncRNA1 might be necessary for fine-tuning of Runx1 function.
To further elucidate the function of Runx1-lncRNA1 in a more physiological setting, we generated a genetically modified mouse line in which this lncRNA is permanently deleted. Our preliminary data show that helper T lymphocytes of this knockout mouse indeed overexpress IL-4 marginally but significantly. At age of 4-5 months, this knockout mouse seems to show evidences of spontaneous infiltration of leukocytes into airway which is observed in Runx1-deficient mouse.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Some of the experiments planned for H25 is not finished yet, but the most important objective of research for H26, the generation of Runx1-lncRNA1 knockout mouse, is already finished.
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| Strategy for Future Research Activity |
Some biochemical studies intended but not finished in H25 will be completed. And the knockout mouse we already generated will be further examined to finish this study.
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