| Project/Area Number |
17K09664
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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 |
Respiratory organ internal medicine
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
萩原 弘一 自治医科大学, 医学部, 教授 (00240705)
海老名 雅仁 東北医科薬科大学, 医学部, 教授 (10280885)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | ムチン / びまん性肺胞障害 / 薬剤性肺障害 / 間質性肺炎急性増悪 / 遺伝子多型 / 次世代シークエンス / MUC4 / 遺伝子解析 / 気道上皮細胞 / 発現ベクター / 遺伝子 / 内科 / 糖鎖 |
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| Outline of Final Research Achievements |
The frequency of "diffuse alveolar disorders," such as severe drug-induced lung injury and acute exacerbation of interstitial pneumonia, is the highest in Japan in the world. Therefore, it was considered that the Japanese population could have a genetic mutation that caused "diffuse alveolar disorder," that is, severe neutrophilic inflammation in the lung. In this research group, we performed association analysis and identified the causative genetic mutation should exist in the variable tandem repeat region of Mucin 4 (MUC4). Next-generation sequences were used to analyze the variable tandem repeat region of MUC4, revealing that the area was divided into conserved parts and three polymorphic sites. Besides, the MUC4 expression vector was prepared for each representative gene polymorphism, and cells stably expressing MUC4 were also made. In the future, we plan to proceed with the functional analysis of MUC4 using these cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は日本人に多い重篤な肺障害の原因遺伝子を同定し、発症予測や予防法、治療法を開発することを目的に行われている。これまでの研究で原因となる遺伝子変異がMucin 4（MUC4）の反復配列領域にあることを明らかにしてきたが次世代シークエンスを使用し、同領域の構造を解明した。また、MUC 4は巨大分子であり培養細胞で解析することが難しかったが、今回、MUC4を完全長で安定に発現する細胞を作成することに成功し、MUC 4の機能解析を培養細胞で行うことを可能にした。
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