Profiling of Gene Expressions Responsible for Acute exacerbation of Idiopathic Pulmonary fibrosis and Its Controling
| Project/Area Number |
17390241
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
EBINA Masahito Tohoku University, Tohoku University graduate School of Medicine, Associate Professor (10280885)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Yasufumi Tohoku University, Inst Development Aging and Cancer, Professor (50178779)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,310,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2007: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2006: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2005: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | idiopathic pulmonary fibrosis / acute exacerbation / Imphatic vessels / alveolar capillaries / inflammatory cytokines / microarray / 肺胞毛細血管 / 突発性肺線維症 / 肺線維芽細胞 / 筋線維芽細胞 / サイトカイン / HMGB1 |
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| Research Abstract |
The pathogenesis of acute exacerbation of idiopathic pulmonary fibrosis remains to be elucidated.
(1) To clarify the mechanisms of acute exacerbation of idiopathic pulmonary fibrosis by detecting the active mediators in alveolar fluids after acute exacerbation and the remodeling of the lungs of these patients. High-mobility group box-1 protein, a chief mediator of acute lung injury, was persistently elevated in the alveolar fluids after acute exacerbation, in positive correlation with monocyte- chemotactic protein, a potent fibrogenic mediator. Intense cytoplasmic staining for monocyte-chemotactic protein, a potent fibrogenic mediator. Intense cytoplasmic staining for high-mobility group box-1 protein was observed in alveolar macrophages and epithelial cells in alveolar-capillary increased lesions where the endothelial cells exhibited remarkably reduced expression of thrombomodulin, an intrinsic antagonist of high-mobility group box-1 protein. We found severe disruption of superficial lymphatics in paraseptal and subpleural tissues where progressive fibrosis developed in these lung tissues. (2) The fibrotic lesions were found to contain myofibroblasts which expressed vasohibin, a negative regulator of angiogenesis and lymphangiogenesis. (3) Mirroarray data and RT-PCR data reveled for the 1^<st> in vitro that myofibroblasts diffentiated from fibroblasts secret vasoibin. Microarray of RNAs in the lungs of patients showed 385 genes differentially expressed. (3) Based on these results we identified anti-fibrotic effects of cyclosporine and early treatment effects of neutrophils elastase inhibitor against acute exacerbation.
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Report
(4 results)
Research Products
(93 results)
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[Journal Article] Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of rats in sepsis2006
Author(s)
Suds K, Kitagawa Y, Ozawa S, Saikawa Y, Ueda M, Ebina M, Yamada S, Hashimoto S, Fukata S, Abraham E, Kitajima M, Ishizaka A.
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Journal Title
World J Surg 30
Pages: 1755-1762
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Contribution of High Mobility Group Box-1 to the Development of Ventilator-induced Lung Injury.2006
Author(s)
Ogawa EN, Ishizaka A, Tasaka S, Koh H, Ueno H, Amaya F, Ebina M, Yamada S, Funakoshi Y, Soejima J, Moriyama K, Kotani T, Hashimoto S, Morisaki H, Abraham E, Takeda J.
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Journal Title
Am J Respir Crit Care Med 174
Pages: 400-407
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of rats in sepsis2006
Author(s)
Suda K, Kitagawa Y, Ozawa S, Saikawa Y, Ueda M, Ebina M, Yamada S, Hashimoto S, Fukata S, Abraham E, Kitajima M, Ishizaka A.
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Journal Title
World J Surg 30
Pages: 1755-1762
Description
「研究成果報告書概要(欧文)」より
Related Report
-
[Journal Article] Contribution of High Mobility Group Box-1 to the Development of Ventilator-induced Lung Injury2006
Author(s)
Ogawa EN, Ishizaka A, Tasaka S, Koh H, Ueno H, Amaya F, Ebina M, Yamada S, Funakoshi Y, Soejima J, Moriyama K, Kotani T, Hashimoto S, Morisaki H, Abraham E, Takeda J.
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Journal Title
Am J Respir Crit Care Med 174
Pages: 400-407
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of rats in sepsis.2006
Author(s)
Suda K, Kitagawa Y, Ozawa S, Saikawa Y, Ueda M, Ebina M, Yamada S, Hashimoto S, Fukata S, Abraham E, Kitajima M, Ishizuka A.
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Journal Title
World Journal of Surgery (In press)
Related Report
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[Journal Article] Hepatocyte growth factor gene transfer to alveolar septa efficiently prevents lung injury by bleomycin.2005
Author(s)
Watanabe M, Ebina M, Nakamura A, Koinuma D, Akiyama K, Maemondo M, Okouchi S, Ota H, Kubota K, Orson FM, Matsumoto K, Nakamura T, and Nukiwa T.
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Journal Title
Molecular Therapy 12
Pages: 58-67
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Granulocyte-macrophage colony stimulating factor and lung immunity in pulmonary alveolar proteinosis.2005
Author(s)
Tazawa R, Hamano E, Ohta H, Arai T, Ishimoto O, Uchida K, Watanabe M, Saito J, Takeshita M, Hirabayashi Y, Ishige I, Eishi Y, Hagiwara K, Ebina M, Inoue Y, Nakata K, Nukiwa T
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Journal Title
Am. J. Respir. Crit. Care Med 171
Pages: 1142-1149
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Granulocyte-macrophage colony stimulating factor and lung immunity in pulmonary alveolar proteinosis2005
Author(s)
Tazawa R, Hamano E, Ohta H, Arai T, Ishimoto O, Uchida K, Watanabe M, Saito J, Takeshita M, Hirabayashi Y, Ishige I, Eishi Y, Hagiwara K, Ebina M, Inoue Y, Nakata K, Nukiwa T.
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Journal Title
Am. J. Respir. Crit. Care Med 171
Pages: 1142-1149
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Hepatocyte growth factor gene transfer to alveolar septa efficiently prevents lung injury by bleomycin2005
Author(s)
Watanabe M, Ebina M, Nakamura A, Koinuma D, Akiyama K, Maemondo M, Okouchi S, Ota H, Kubota K, Orson FM, Matsumoto K, Nakamura T, and Nukiwa T.
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Journal Title
Molecular Therapy 12
Pages: 58-67
Description
「研究成果報告書概要(欧文)」より
Related Report
-
[Journal Article] Granulocyte-macrophage colony stimulating factor and lung immunity in pulmonary alveolar proteinosis.2005
Author(s)
Tazawa R, Hamano E, Ohta H, Arai T, Ishimoto O, Uchida K, Watanabe M, Saito J, Takeshita M, Hirabayashi Y, Ishige I, Eishi Y, Hagiwara K, Ebina M, Inoue Y, Nakata K, Nukiwa T.
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Journal Title
Am.J.Respir.Crit.Care Med 171
Pages: 1142-1149
Related Report
-
[Journal Article] Hepatocyte growth factor gene transfer to alveolar septa efficiency pervents lung injury by bleomycin.2005
Author(s)
Watanabe M, Ebina M, Nakamura A, Koinuma D, akiyama K, Maemondo M, Okouchi S, Ota H, Kubota K, Orson FM, Matsumoto K, Nakamura T, Nukiwa T.
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Journal Title
Molecular Therapy 12
Pages: 58-67
Related Report
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