2007 Fiscal Year Final Research Report Summary
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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| Keywords | idiopathic pulmonary fibrosis / acute exacerbation / Imphatic vessels / alveolar capillaries / inflammatory cytokines / microarray |
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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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[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
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
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
-
[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
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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
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
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
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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
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