Clarification of pathogenesis in chronic obstructive pulmonary disease focusing on lung resident cells.
Project/Area Number |
26293195
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Tohoku University |
Principal Investigator |
Sugiura Hisatoshi 東北大学, 医学(系)研究科(研究院), 准教授 (20445092)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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Keywords | 酸化型コレステロール / 細胞老化 / 転写因子 / KLF5 / 活性硫黄分子種 / 成長因子 / レドックス / 液性因子 / 還元物質 / 肺構築細胞 / COPD / オキシステロール / 活性酸素種 / 活性窒素種 / 肺線維芽細胞 |
Outline of Final Research Achievements |
We demonstrated the followings. Production of 27-OHC was enhanced in the patients with COPD. Treatment with 27-OHC accelerated cellular senescence of lung resident cells and chronic exposure of 27-OHC impaired fibroblast-mediated tissue repair function. Bronchial fibroblasts from COPD patients showed marked pro-fibrotic feature compared to those from control subjects. KLF-5 regulated the profibrotic effects in the cells and expression of KLF-5 was enhanced in the peribronchial lesion of small airways of COPD patients. We demonstrated that production of newly identified anti-oxidants, reactive persulfides species was reduced in the lungs of COPD patients compared with healthy controls. We found that the plasma levels of GDF11, which is an anti-senescent factor, were decreased in COPD patients compared with healthy subjects.
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Report
(4 results)
Research Products
(50 results)
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[Journal Article] Japanese guidelines for adult asthma 20172017
Author(s)
Ichinose M, Sugiura H, Nagase H, Yamaguchi M, Inoue H, Sagara H, Tamaoki J, Tohda Y, Munakata M, Yamauchi K, Ohta K; Japanese Society of Allergology.
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Journal Title
Allergology International
Volume: 66
Issue: 2
Pages: 163-189
DOI
NAID
ISSN
1323-8930, 1440-1592
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Exome sequencing deciphers a germline MET mutation in familial epidermal growth factor receptor-mutant lung cancer.2017
Author(s)
Tode N, Kikuchi T, Sakakibara T, Hirano T, Inoue A, Ohkouchi S, Tamada T, Okazaki T, Koarai A, Sugiura H, Niihori T, Aoki Y, Nakayama K, Matsumoto K, Matsubara Y, Yamamoto M, Watanabe A, Nukiwa T, Ichinose M.
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Journal Title
Cancer Sci
Volume: 印刷中
Issue: 6
Pages: 1263-1270
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Possible role of Krüppel-like factor 5 in the remodeling of small airways and pulmonary vessels in chronic obstructive pulmonary disease.2016
Author(s)
Abe. K., H. Sugiura, Y. Hashimoto, T. Ichikawa, A. Koarai, M. Yamada, T. Numakura, K. Onodera, R. Tanaka, K. Sato, S. Yanagisawa, T. Okazaki, T. Tamada, T. Kikuchi and M. Ichinose.
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Journal Title
Respir Res
Volume: 17
Issue: 1
Pages: 7-7
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] 27-hydroxycholesterol accelerates cellular senescence in human lung resident cells.2016
Author(s)
Hashimoto Y, Sugiura H, Togo S, Koarai A, Abe K, Yamada M, Ichikawa T, Kikuchi T, Numakura T, Onodera K, Tanaka R, Sato K, Yanagisawa S, Okazaki T, Tamada T, Kikuchi T, Hoshikawa Y, Okada Y, Ichinose M.
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Journal Title
Am J Physiol Lung Cell Mol Physiol
Volume: 310
Issue: 11
Pages: L1028-L1041
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Serum extracellular vesicular miR-21-5p is a predictor of the prognosis in idiopathic pulmonary fibrosis.2016
Author(s)
Makiguchi T, Yamada M, Yoshioka Y, Sugiura H, Koarai A, Chiba S, Fujino N, Tojo Y, Ota C, Kubo H, Kobayashi S, Yanai M, Shimura S, Ochiya T, Ichinose M.
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Journal Title
Respir Res
Volume: 17
Issue: 1
Pages: 110-110
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Extracellular ATP is involved in dsRNA-induced MUC5AC production via P2Y2R in human airway epithelium.2016
Author(s)
Shishikura Y, Koarai A, Aizawa H, Yamaya M, Sugiura H, Watanabe M, Hashimoto Y, Numakura T, Makiguti T, Abe K, Yamada M, Kikuchi T, Hoshikawa Y, Okada Y, Ichinose M.
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Journal Title
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Cigarette smoke augments MUC5AC production via the TLR3-EGFR pathway in airway epithelial cells.2015
Author(s)
K. Kanai, A. Koarai, Y.Shishikura, H. Sugiura, T. Ichikawa, T. Kikuchi, K. Akamatsu, T. Hirano, M. Nakanishi, K. Matsunaga, Y. Minakata and M.Ichinose.
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Journal Title
Respir Investig.
Volume: in press
Issue: 4
Pages: 137-148
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Reduced level of physical activity in Japanese patients with chronic obstructive pulmonary disease2014
Author(s)
Minakata Y, Sugino A, Kanda M, Ichikawa T, Akamatsu K, Koarai A, Hirano T, Nakanishi M, Sugiura H, Matsunaga K, Ichinose M
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Journal Title
Respiratory investigation
Volume: 52
Issue: 1
Pages: 41-48
DOI
Related Report
Peer Reviewed
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[Journal Article] Sphingosylphosphorylcholine induces α-smooth muscle actin expression in human lung fibroblasts and fibroblasts mediated gel contraction via S1P2 receptor and Rho/Rho-kinase pathway.2014
Author(s)
Wang XQ, Mao LJ, Fang QH, Kobayashi T, Kim HJ, Sugiura H, Kawasaki S, Togo S, Kamio K, Liu X, Rennard SI.
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Journal Title
Prostaglandins Other Lipid Mediat
Volume: 108
Pages: 23-30
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Matrix metalloproteinase-9 activates TGF-β and stimulates fibroblast contraction of collagen gels.2014
Author(s)
Kobayashi T, Kim H, Liu X, Sugiura H, Kohyama T, Fang Q, Wen FQ, Abe S, Wang X, Atkinson JJ, Shipley JM, Senior RM, Rennard SI.
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Journal Title
Am J Physiol Lung Cell Mol Physiol.
Volume: 306
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] TLR3 activation augments matrix metalloproteinase production through reactive nitrogen species generation in human lung fibroblasts.2014
Author(s)
Ichikawa T, Sugiura H, Koarai A, Minakata Y, Kikuchi T, Morishita Y, Oka A, Kanai K, Kawabata H, Hiramatsu M, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Yamamoto N, Ichinose M.
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Journal Title
J Immunol
Volume: 192
Issue: 11
Pages: 4977-4988
DOI
Related Report
Peer Reviewed
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[Presentation] Oxidattive stress and COPD2016
Author(s)
H. Sugiura.
Organizer
016. 9th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
Place of Presentation
Sendai (Sendai International Center)
Related Report
Int'l Joint Research / Invited
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[Presentation] 気道の酸化ストレス評価2014
Author(s)
杉浦久敏
Organizer
第25回日本アレルギー学会総会春季臨床大会
Place of Presentation
国立京都国際会館(京都府)
Year and Date
2014-05-09
Related Report
Invited
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