Evaluating the role of the lung microbiome in pulmonary fibrosis
Project/Area Number |
18K08175
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53030:Respiratory medicine-related
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Research Institution | Mie University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
小林 哲 三重大学, 医学部附属病院, 准教授 (20437114)
Gabazza Esteban 三重大学, 医学系研究科, 教授 (00293770)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | IPF / fibrosis / microbiome / 肺線維症 / 細菌叢 / TGF-β / 16S RNA / マウスモデル |
Outline of Final Research Achievements |
In the present investigation we developed a genetically engineered mouse model that expresses specifically in the lung the full-length of the human TGF-β1 gene. The mouse model spontaneously develops chronic pulmonary fibrosis. We evaluated the role of the lung microbiome in pulmonary fibrosis using this mouse model. We discovered that the fibrotic lung tissue has high concentration of salt and that bacteria of the Staphylococcus genera that grow when the fibrotic lung tissue is cultured under hypersaline conditions secrete a pro-apoptotic peptide. This peptide induces apoptosis of alveolar epithelial cell lines in vitro and promotes the death of alveolar epithelial cells in the transgenic mouse of pulmonary fibrosis. Overall, the results of this investigation showed that a bacterium from the lung microbiome secretes a deadly peptide that causes apoptosis of lung alveolar cells. This novel peptide may be a good target for the development of a novel therapy for pulmonary fibrosis.
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Academic Significance and Societal Importance of the Research Achievements |
呼吸器疾患に関する細菌叢の検討は報告数も少なく、研究は始まったばかりである。呼吸器疾患の中で特発性肺線維症は悪性腫瘍と比較しても予後不良な難治性肺疾患である。本研究は肺の線維化の発症および進展を含めた病態への細菌叢の役割を明らかにするものであり、その機構が明らかになれば臨床応用にも期待がもてる画期的な研究である。今回の研究で同定されたブドウ球菌から分泌されるペプチドは肺線維症におけるアポトーシスに関与している可能性があり、新たなバイオマーカーの開発や治療標的となりうると考えられる。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Factors leading to failure to diagnose pulmonary malignant tumors using endobronchial ultrasound with guide sheath within the target lesion.2019
Author(s)
Nishii Y, Yasuma T, Ito K, Suzuki Y, Watanabe F, Kobayashi T, Nishihama K, D'Alessandro-Gabazza CN, Fujimoto H, Gabazza EC, Asano F, Taguchi O, Hataji O.
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Journal Title
Respir Res.
Volume: 20
Issue: 1
Pages: 207-207
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Protective Role of Matrix Metalloproteinase-2 in Allergic Bronchial Asthma.2019
Author(s)
Takahashi Y, Kobayashi T, D'Alessandro-Gabazza CN, Toda M, Fujiwara K, Okano T, Fujimoto H, Asayama K, Takeshita A, Yasuma T, Nishihama K, Inoue R, Qin L,Takei Y, Taguchi O, Gabazza EC.
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Journal Title
Front Immunol.
Volume: 10
Pages: 1795-1795
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Protein S is Protective in Acute Lung Injury by Inhibiting Cell Apoptosis.2019
Author(s)
Baffour Tonto P, Yasuma T, Kobayashi T, D'Alessandro-Gabazza CN, Toda M, Saiki H, Fujimoto H, Asayama K, Fujiwara K, Nishihama K, Okano T, Takeshita A, Gabazza EC.
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Journal Title
Int J Mol Sci.
Volume: 20
Pages: 1082-1082
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of Halophilic Microbes in Lung Fibrotic Tissue by Oligotyping2018
Author(s)
D’Alessandro-Gabazza Corina N.、Méndez-García Celia、Hataji Osamu、Westergaard Sara、Watanabe Fumiaki、Yasuma Taro、Toda Masaaki、Fujimoto Hajime、Nishihama Kota、Fujiwara Kentaro、Taguchi Osamu、Kobayashi Tetsu、Mackie Roderick I.、Cann Isaac、Gabazza Esteban C.
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Journal Title
Frontiers in Microbiology
Volume: 9
Pages: 1892-1892
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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