Elucidation of the pathophysiology of pulmonary fibrosis and development of new treatments by applying metabolome analysis
| Project/Area Number |
18K08136
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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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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
黒澤 一 東北大学, 事業支援機構, 教授 (60333788)
岡田 克典 東北大学, 加齢医学研究所, 教授 (90323104)
兼平 雅彦 東北大学, 大学病院, 助教 (90374941)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 間葉系幹細胞 / Stanniocalcin-1 / 抗酸化作用 / 抗線維化作用 / 抗炎症作用 / 翻訳後修飾 / SOCS1 / SMAD7 / 脱共役呼吸 / 間質性肺炎 / 肺障害 / 治療 / 新型コロナウイルス感染症 / 吸入療法 / エピゲノム / メタボローム / 肺線維症 |
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| Outline of Final Research Achievements |
Since the mesenchymal stem cell (MSC) -derived humoral factor Stanniocalcin-1 (STC1) regulates mitochondrial membrane potential, the effect of the addition or inhalation of STC1 on the central metabolic pathway were evaluated in cells and bleomycin inhalation mice model using comprehensive metabolomics analyses and specific measurements against each substance. We revealed STC1 affects the TCA, β-oxidation, methionine and glutathione pathway. These results explained the antioxidant effect of STC1 and suggested a relationship with post-translational modification (epigenetics). From additional experiments, we revealed that STC1 induced SOCS1 / SMAD7 demethylation and histone / SMAD7 acetylation. Furthermore, SOCS1 suppressed the JAK / STAT pathway and SMAD7 suppressed the TGFβ / SMAD pathway in cells and animal model. From the above, it was shown that STC1 may be used for the treatment of COVID19, autoimmune diseases, and fibrotic diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
STC1によるの難病治療への可能性を示したことが本研究成果の意義である。STC1経気道投与の特徴は、①細胞代謝と翻訳後修飾の相互関連に着目した新規作用機序、②生体物質であり、経気道投与が可能であることにより得られる高い安全性、③HEK293細胞を利用したリコンビナントタンパクとして、安価、簡便に得ることが可能であること、等である。用途として、①新型コロナウイルス感染症の感染予防薬・重症化予防及び治療、②JAK/STATが関連する関節リウマチ等の自己免疫疾患に対する治療、③TGFβ/SMADが関連する特発性肺線維症等の線維性疾患に対する治療などが考えられる。本研究に関して特許を出願中である。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Kobayashi K, Ohkouchi S, Sasahara Y, Ebina M, Nakata K, Saito R, Akiba M, Sado T, Oishi H, Watanabe T, Kurosawa H, Okada Y. Improvement of native pulmonary alveolar proteinosis after contralateral single living-donor lobar lung transplantation: A case report.2020
Author(s)
Kobayashi K, Ohkouchi S, Sasahara Y, Ebina M, Nakata K, Saito R, Akiba M, Sado T, Oishi H, Watanabe T, Kurosawa H, Okada Y.
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Journal Title
Pediatr Transplant
Volume: 24
Issue: 2
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhaled GM-CSF for Pulmonary Alveolar Proteinosis2019
Author(s)
Tazawa R、Ueda T、Abe M、Tatsumi K、Eda R、Kondoh S、Morimoto K、Tanaka T、Yamaguchi E、Takahashi A、Oda M、Ishii H、Izumi S、Sugiyama H、Nakagawa A、Tomii K、Suzuki M、Konno S、Ohkouchi S、Tode N、Handa T、Hirai T、Inoue Y、Arai T、Asakawa K、Sakagami T、Hashimoto A、Tanaka T、Takada T、Mikami A、Kitamura N、Nakata K
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Journal Title
New England Journal of Medicine
Volume: 381
Issue: 10
Pages: 923-932
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Respiratory resistance among adults in a population-based cohort study in Northern Japan.2019
Author(s)
Miura E, Tsuchiya N, Igarashi Y, Arakawa R, Nikkuni E, Tamai T, Tabata M, Ohkouchi S, Irokawa T, Ogawa H, Takai-Igarashi T, Suzuki Y, Kuriyama S, Tamiya G, Hozawa A, Yamamoto M, Kurosawa H.
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Journal Title
Respiratory Investigation
Volume: 印刷中
Issue: 3
Pages: 30226-0
DOI
Related Report
Peer Reviewed
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[Journal Article] Peripheral alveolar nitric oxide concentration reflects alveolar inflammation in autoimmune pulmonary alveolar proteinosis.2018
Author(s)
Hirano T, Ohkouchi S, Tode N, Kobayashi M, Ono M, Satoh T, Mitsuishi Y, Watanabe A, Tabata M, Irokawa T, Ogawa H, Sugiura H, Kikuchi T, Akasaka K, Tazawa R, Inoue Y, Nakata K, Kurosawa H, Ichinose M.
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Journal Title
ERJ open research
Volume: 4
Issue: 1
Pages: 00071-2017
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Book] Disaster and Respiratory Disease2018
Author(s)
Shinya Ohkouchi, Shinsuke Yamanda, Shu Hisata, Masao Tabata, Toshiya Irokawa, Hiromasa Ogawa, Hajime Kurosawa, Kohei Yamauchi, Keisaku Fujimoto
Total Pages
178
Publisher
Springer
ISBN
9789811325977
Related Report
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