The role of FUT8 in the development of chronic obstructive pulmonary disease
Project/Area Number |
23591118
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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 | Osaka University |
Principal Investigator |
GAO CONGXIAO 大阪大学, 産業科学研究所, 招へい教員 (50379260)
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Project Period (FY) |
2011 – 2013
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 慢性閉塞性肺疾患 / FUT8 / 喫煙暴露 / コアフコース / TGFβ / Fut8ヘテロ欠損マウス / alpah 1,6 fucose / alpha 1,6 fucose |
Research Abstract |
The physiological relevance of core fucosylation in the pathogenesis of COPD was investigated using cigarette smoke exposed Fut8 heterozygous knockout mice. A marked decrease in FUT8 activity and elevated matrix metalloproteinase (MMP)-9 activities were observed at an early stage of exposure. Emphysema developed in only half the exposed-period required for wild type mice. TGF-beta1-Smad2 signaling pathway has lost its function. Moreover, our investigation showed that, among symptomatic current or ex-smokers with stable COPD or at risk outpatients (n=226), a faster annual decline of the forced expiratory volume in 1s (FEV1) was significantly associated with lower FUT8 activity. Patients with lower FUT8 activity experienced exacerbations more frequently. These data suggest that reduced FUT8 activity is associated with the progression of COPD and serum FUT8 activity is a minimally invasive predictive biomarker for progression and exacerbation of COPD.
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Sensitivity of Heterozygous α1,6-Fucosyltransferase Knock-out Mice to Cigarette Smoke-induced Emphysema: IMPLICATION OF ABERRANT TRANSFORMING GROWTH FACTOR-β; SIGNALING AND MATRIX METALLOPROTEINASE GENE EXPRESSION.2012
Author(s)
Gao C, Maeno T, Ota F, Ueno M, Korekane H, Takamatsu S, Shirato K, Matsumoto A, Kobayashi S, Yoshida K, Kitazume S, Ohtsubo K, Betsuyaku T, Taniguchi N
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Journal Title
J. Biol. Chem.
Volume: 287(20)
Issue: 20
Pages: 16699-16708
DOI
Related Report
Peer Reviewed
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[Journal Article] α1,6-Fucosyltransferase (Fut8) is implicated in vulnerability to elastase-induced emphysema in mice and a possible non-invasive predictive marker for disease progression and exacerbations in chronic obstructive pulmonary disease (COPD).2012
Author(s)
Kamio K, Yoshida T, Gao C, Ishii T, Ota F, Motegi T, Kobayashi S, Fujinawa R, Ohtsubo K, Kitazume S, Angata T, Azuma A, Gemma A, Nishimura M, Betsuyaku T, Kida K, Taniguchi N.
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 424(1)
Issue: 1
Pages: 112-117
DOI
Related Report
Peer Reviewed
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[Presentation] Sensitivity of heterozygous a1, 6-fucosyltransferase knock out mice to cigarette smoke-induced emphysema: Implication of aberrant TGF-b signaling and MMP gene expression.2012
Author(s)
Gao C, Maeno T, Ota F, Korekane H, Takamatsu S, Kobayashi S, Yoshida K, Kitazume S, Ohtsubo K, Taniguchi N
Organizer
GlycoT 2012
Place of Presentation
Hannover, Germany
Related Report
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