2023 Fiscal Year Final Research Report
Identification of the gene responsible for pulmonary fibrosis, and exploration about the association between cell death and fibrosis through the disease-derived iPS cell-differentiated lung cells
Project/Area Number |
20H03687
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 53030:Respiratory medicine-related
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Setoguchi Yasuhiro 東京医科歯科大学, 大学院医歯学総合研究科, 特任教授 (90206649)
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Co-Investigator(Kenkyū-buntansha) |
宮崎 泰成 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30396999)
後藤 慎平 京都大学, iPS細胞研究所, 教授 (50747219)
岡本 師 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (60724200)
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Project Period (FY) |
2020-04-01 – 2024-03-31
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Keywords | 家族性間質性肺炎 / サーファクタント / 遺伝子 / エクソーム解析 / 小胞体ストレス / 細胞死 / iPS細胞 / 肺胞II型表皮細胞 |
Outline of Final Research Achievements |
To investigate the causes of familial interstitial lung disease, we identified the surfactant protein A (SFTPA) and C (SFTPC) genes. We found that mutations in these genes induce two different types of cell death, necroptosis and apoptosis, in type II alveolar epithelial cells. By developing a system to quantify ER stress, we discovered that the level of stress varies according to genetic mutations and that this can affect clinical pathology. In addition, the study showed that lung epithelial cells derived from iPS cells created from the peripheral blood of each patient have the potential to be analysed as an alternative to cells obtained from lung biopsies. It may be useful for the development of therapeutic drugs to quantify ER stress and disease-derived iPS cells.
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Free Research Field |
呼吸器内科
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Academic Significance and Societal Importance of the Research Achievements |
ER stressの定量化システムによってSFTPA1/A2, SFTPCの変異によってER stressの違いがあることを明らかにし、ER stressによる細胞死の種類が異なることは新規の知見である。肺線維症においてER stressは遺伝子変異にかかわらず認められることも考え合わせるとER stressの定量化は、治療候補薬物の大規模スクリーニングへの応用が可能となる。また、患者由来iPS細胞からの各種肺細胞への分化誘導が可能となり線維化発症の機序解明だけでなくER stress定量化システムとの併用で間質性肺疾患のprecision medicine構築も可能となる意義がある。
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