Identification and application of therapeutic targets and diagnostic markers of obstructive pulmonary diseases based on global expression analysis
Project/Area Number |
25460102
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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 |
Pharmacology in pharmacy
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Research Institution | Kumamoto University |
Principal Investigator |
Shuto Tsuyoshi 熊本大学, 生命科学研究部(薬), 准教授 (80333524)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | 閉塞性肺疾患 / プロテアーゼ / 参加ストレス / ビタミンC / マイクロアレイ / 遺伝子 / 慢性炎症 / 粘液貯留 |
Outline of Final Research Achievements |
Protease-antiprotease imbalance and oxidative stress are considered to be major pathophysiological hallmarks of severe lung diseases including chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), but their role in the regulation of pulmonary emphysema and dysfunction of βENaC-transgenic (Tg) mice, a murine model of COPD/CF, is unknown. DNA microarray analysis revealed that protease- and oxidative stress-dependent pathways are activated in the lung tissue of βENaC-Tg mice. Here, treatments of βENaC-Tg mice with a serine protease inhibitor ONO3403 and an antioxidant N-acetylcystein significantly improved pulmonary emphysema and dysfunction. Moreover, depletion of a murine endogenous antioxidant Vitamin C (VC), by genetic disruption of VC-synthesizing enzyme SMP30 in βENaC-Tg mice, increased inflammatory status in lung tissue and exaggerated pulmonary emphysema with a significant decrease in pulmonary function, possibly due to an increased oxidative stress.
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Report
(4 results)
Research Products
(49 results)
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[Journal Article] Endoplasmic Reticulum (ER) Stress Induces Sirtuin 1 (SIRT1) Expression via the PI3K-Akt-GSK3β Signaling Pathway and Promotes Hepatocellular Injury.2015
Author(s)
Koga T, Suico MA, Shimasaki S, Watanabe E, Kai Y, Koyama K, Omachi K, Morino-Koga S, Sato T, Shuto T, Mori K, Hino S, Nakao M, Kai H.
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Journal Title
J Biol Chem.
Volume: 290
Issue: 51
Pages: 30366-30374
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Lipopolysaccharide decreases single immunoglobulin interleukin-1 receptor-related molecule (SIGIRR) expression by suppressing Sp1 via TLR4-p38 pathway in monocytes and neutrophils.2014
Author(s)
Ueno-Shuto K, Kato K, Tasaki Y, Sato M, Sato K, Uchida Y, Sakai H, Ono T, Suico MA, Mitsutake K, Tokutomi N, Kai H, Shuto T.
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Journal Title
J Biol Chem.
Volume: 289(26)
Pages: 18097-18109
Related Report
Peer Reviewed
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[Journal Article] Mild electrical stimulation at 0.1-ms pulse width induces p53 protein phosphorylation and G2 arrest in human epithelial cells.2013
Author(s)
Fukuda ft, Suico MA, Koyama K, Omachi K, Kai Y, Matsuyama S, Mitsutake K, Taura M, Mo rino-Koga S, Shuto T, Kai H.
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Journal Title
Journal of Biological Chemistry
Volume: 288(22)
Issue: 22
Pages: 16117-16126
DOI
Related Report
Peer Reviewed
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[Presentation] Pharmacological and genetic approaches determine protease and oxidative stress as exacerbating factors in a mouse model of obstructive lung diseases2015
Author(s)
T. Shuto, S. Kamei, H. Nohara, H. Fujikawa, Y. Sakaguchi, C. Matsumoto, T. Ono, T. Sugahara, M.A. Suico, K. Mitsutake, H. Kai
Organizer
International Symposium on Chronic Inflammatory Diseases, Kumamoto
Place of Presentation
熊本大学薬学部(熊本県熊本市)
Year and Date
2015-10-16
Related Report
Int'l Joint Research / Invited
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[Presentation] Physiological and pathophysiological induction of pulmonary mucus hypersecretionby GLP-1 receptor agonist Exendin-42015
Author(s)
H. Nohara, R. Nakashima, T. Shuto, S. Kamei, H. Fujikawa, K. Maruta, C. Matsumoto, Y. Sakaguchi, M. Suico, D.C. Gruenert, H. Kai
Organizer
International Symposium on Chronic Inflammatory Diseases, Kumamoto
Place of Presentation
熊本大学薬学部(熊本県熊本市)
Year and Date
2015-10-16
Related Report
Int'l Joint Research
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[Presentation] The effect of Uricase inhibitor on respiratory function and emphysema in murine models of obstructive pulmonary disease2015
Author(s)
H. Fujikawa, T. Shuto, S. Kamei, H. Nohara, K. Maruta, R. Nakashima, M. Suico, T. Takeo, N. Nakagata, H. Kai
Organizer
International Symposium on Chronic Inflammatory Diseases, Kumamoto
Place of Presentation
熊本大学薬学部(熊本県熊本市)
Year and Date
2015-10-16
Related Report
Int'l Joint Research
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[Presentation] The pharmacological evaluation of expectorant in mucous obstructive pulmonary disease mouse model2013
Author(s)
Y. Sakaguchi, T. Shuto, S. Kamei, H. Nohara, C. Matsumoto, T. Ono, M. A. Suico, H. Kai
Organizer
2013 ASCB Annual Meeting
Place of Presentation
The New Orleans Ernest N. Morial Convention Center, New Orleans, Lousiana,USA
Related Report
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