The role of FUT8 in the development of chronic obstructive pulmonary disease

• Project/Area Number: 23591118
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• 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)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥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.

Research Products

• [Journal Article] Flagellin/Toll-like receptor 5 response was specifically attenuated by keratan sulfate disaccharide via decreased EGFR phosphorylation in normal human bronchial epithelial cells (2013)
  • Author(s): Shirato K, Gao C, Ota F, Angata T, Shogomori H, Ohtsubo K, Yoshida K, Lepenies B, Taniguchi N
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 435(3) Issue: 3 Pages: 460-465
  • DOI: 10.1016/j.bbrc.2013.05.009
  • Peer Reviewed
• [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
  • Journal Title: J. Biol. Chem. Volume: 287(20) Issue: 20 Pages: 16699-16708
  • DOI: 10.1074/jbc.m111.315333
  • Peer Reviewed
• [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.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 424(1) Issue: 1 Pages: 112-117
  • DOI: 10.1016/j.bbrc.2012.06.081
  • Peer Reviewed
• [Journal Article] Sensitivity of heterozygous α1, 6- fucosyltransferase knock out mice to cigarette smoke-induced emphysema: implication of aberrant TGF-β signaling and MMP gene expression. (2012)
  • Author(s): Gao C, Maeno T, Taniguchi N, et al.
  • Journal Title: Journal of Biological Chemistry Volume: 287
  • Peer Reviewed
• [Presentation] Lowered level of core fucosylation is a possible non-invasive predictive marker for chronic obstructive pulmonary disease (COPD) (2013)
  • Author(s): Gao, C.
  • Organizer: 22nd International Symposium on Glycoconjugates (GLYCO XXII)
  • Place of Presentation: Dailian China
• [Presentation] Lowered level of core fucosylation is a possible non-invasive predictive marker for chronic obstructive pulmonary disease (COPD) (2013)
  • Author(s): Gao C, Kamio K, Ota F., Ishii T., Kida K., Taniguchi N.
  • Organizer: Glyco 22
  • Place of Presentation: 中国大連
• [Presentation] Sensitivity of heterozygous a1, 6-fucosyltransferase knock out mice to cigarette smoke-induced emphysema : Implication of aberrant TGF-βsignaling and MMP gene expression (2012)
  • Author(s): Gao, C.
  • Organizer: 8th International Symposium on Glycosyltransferases
  • Place of Presentation: Hannover, Germany
• [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
• [Presentation] alpha1,6-Fucosyltransferase (Fut8) is implicated in vulnerability to smoke-induced emphysema in mice and a possible non-invasive predictive marker for human chronic obstructive pulmonary disease (COPD). (2012)
  • Author(s): Gao C, Kamio K, Ota F, Ishii T, Kobayashi S, Kida K, Taniguchi N
  • Organizer: Joint Meeting of the Society for Glycobiology and American Society for Marix Biology
  • Place of Presentation: San Diego, USA
• [Presentation] Molecular mechanism of the high susceptibility of alpha 1,6 fucosyltransferase (Fut8) heterozygous knockout mice to cigarette smoke-induced emphysema (2011)
  • Author(s): Gao, C.
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] Fut8遺伝子変異マウスにおける慢性閉塞性肺疾患早期発症の分子機構の解明 (2011)
  • Author(s): 高 叢笑
  • Organizer: 第84回に本生化学会大会
  • Place of Presentation: 京都
• [Book] Biological functions of branched N-glycans related to physiology and pathology of extracellular matrix.Extracellular Matrix: Pathobiology and Signaling (2012)
  • Author(s): Gao C, Ohtsubo K, Gu J, and Taniguchi N
  • Total Pages: 890
  • Publisher: DE GRUYTER
• [Remarks] 掲載新聞名:日刊工業新聞 平成24年4月6日(金曜日)
• [Remarks] 掲載新聞名:化学工業日報 平成24年4月9日(月曜日)
• [Remarks] 掲載新聞名:科学新聞 平成24年4月16日(月曜日)
• [Remarks] 掲載新聞名:薬事日報 平成24年4月20日(金曜日)
• [Remarks] 掲載ホームページ名、URL:理化学研究所プレスリリース
  • URL: http://www.riken.go.jp/r-world/research/results/2012/120404/index.html