Development of novel therapeutic approaches for pulmonary fibrosis using MUC5B overexpressing mice
Project/Area Number |
17K09611
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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 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Mie University |
Principal Investigator |
Taguchi Osamu 三重大学, 医学系研究科, リサーチアソシエイト (90197244)
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Co-Investigator(Kenkyū-buntansha) |
GABAZZA CORINA 三重大学, 医学系研究科, 特任講師(研究担当) (10750656)
戸田 雅昭 三重大学, 医学系研究科, 講師 (10202201)
小林 哲 三重大学, 医学部附属病院, 准教授 (20437114)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 肺線維症 / ムチン / トランジェニックマウス / ブレオマイシン / サイトカイン / PCR成長因子 / ケモカイン / コラーゲン / 細菌叢 / MUC5B / rs35705950単塩基多型 / 遺伝子改変マウス / TGFbeta1 / 肺傷害 / 成長因子 / 遺伝子変異 |
Outline of Final Research Achievements |
Several studies reported the association of MUC5B promoter variant rs35705950 with idiopathic pulmonary fibrosis. Here we developed a transgenic mouse overexpressing the human MUC5B promoter variant rs35705950 and evaluated whether its overexpression correlates with the development of experimental pulmonary fibrosis. We compared the degree of lung fibrosis and fibrotic markers between wild type and rs35705950 transgenic mice. Lung fibrosis was induced by bleomycin using osmotic minipumps. The number of inflammatory cells, the hydroxyproline content, the concentration of extracellular matrix proteins and the level of transforming growth factor-beta1 in the lungs were significantly enhanced in wild-type mice compared to MUC5B transgenic mice receiving bleomycin. The results of this suggest that overexpression of MUC5B protein in the lungs protects against bleomycin-induced pulmonary fibrosis.
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Academic Significance and Societal Importance of the Research Achievements |
肺線維症は世界的に増加しているが、特に日本ではその傾向は著しい。また、急性間質性肺炎、特発性器質化肺炎など、過剰な線維芽細胞の増殖が、その病態の主体をなす疾患も増加しつつあり、現在の治療薬に対する抵抗性の難治例も多い。従って、特に日本では、新しいより有効な治療法の開発が急務であり、MUC5Bはその有力な候補になりうると考えられる。従って本研究で得た成果は、世界に先駆けての抗線維化剤の開発において画期的な基礎的情報を提供するものと期待される。
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Report
(4 results)
Research Products
(41 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] Renal Injury during Long-Term Crizotinib Therapy2018
Author(s)
Yasuma Taro、Kobayashi Tetsu、D’Alessandro-Gabazza Corina、Fujimoto Hajime、Ito Kentaro、Nishii Yoichi、Nishihama Kota、Baffour Tonto Prince、Takeshita Atsuro、Toda Masaaki、Gabazza Esteban、Taguchi Osamu、Yonemura Shigenori、Hataji Osamu
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Journal Title
International Journal of Molecular Sciences
Volume: 19
Issue: 10
Pages: 2902-2902
DOI
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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[Journal Article] A Retrospective Comparison of the Clinical Efficacy of Gefitinib, Erlotinib and Afatinib in Japanese Patients with Non-small Cell Lung Cancer2018
Author(s)
Fujiwara A, Yoshida M, Fujimoto H, Nakahara H, Ito K, Nishihama K, Yasuma T, Hataji O, Taguchi O, D'Alessandro-Gabazza CN, Gabazza EC, Kobayashi T
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Journal Title
Oncol Res
Volume: 印刷中
Issue: 7
Pages: 1031-1036
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Smart watch-based coaching with tiotropium and olodaterol ameliorates physical activity in patients with chronic obstructive pulmonary disease2017
Author(s)
Hataji O, Nishii Y, Ito K, Sakaguchi T, Saiki H, Suzuki Y, D'Alessandro-Gabazza C, Fujimoto H, Kobayashi T, Gabazza EC, Taguchi O
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Journal Title
Exp Ther Med
Volume: 14
Pages: 4061-4064
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Oligonucleotide-targeting periostin ameliorates pulmonary fibrosis2017
Author(s)
Tomaru A、Kobayashi T、Hinneh J A、Baffour Tonto P、D'Alessandro-Gabazza C N、Fujimoto H、Fujiwara K、Takahashi Y、Ohnishi M、Yasuma T、Nishihama K、Yoshino M、Takao K、Toda M、Totoki T、Takei Y、Yoshikawa K、Taguchi O、Gabazza E C
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Journal Title
Gene Ther
Volume: 24
Issue: 11
Pages: 706-716
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Creating a prediction formula for resting energy consumption of patients with COPD and ILD2018
Author(s)
Keisuke Morikawa, Yasunori Imaoka, Hiroyuki Takemura, Kana Kitayama, Shunta Shimoda, Shogo Inaba, Haruka Kusuki, Yu Hashitsume, Momoko Hirose, Yuta Suzuki, Makoto Okada, Corina N. D’Alessandro-Gabazza, Esteban Gabazza, Osamu Taguchi, Osamu Hataji
Organizer
ERS 2018 International Congress
Related Report
Int'l Joint Research
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[Presentation] Coagulation markers in COPD2018
Author(s)
Gunnar Reksten Husebo, Esteban Gabazza, Corina D'Alessandro, Marianne Aanerud, Masaaki Toda, Rune Gronseth, Per S. Bakke, Tomas Mikal Lind Eagan
Organizer
ERS 2018 International Congress
Related Report
Int'l Joint Research
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