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

2013 Fiscal Year Final Research Report

• 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
• Keywords: 慢性閉塞性肺疾患 / FUT8 / 喫煙暴露 / コアフコース / TGFβ

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] Sensitivity of heterozygous alpha1,6-fucosyltransferase knock-out mice to cigarette smoke-induced emphysema : implication of aberrant transforming growth factor-beta 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., and Taniguchi, N.
  • Journal Title: J Biol Chem. Volume: 287 Pages: 16699-16708
  • DOI: 10.1074/jbc.M111.315333
  • Peer Reviewed
• [Journal Article] alpha1,6-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., Azuma, A., Gemma, A., Nishimura, M., Betsuyaku, T., Kida, K., and Taniguchi, N.
  • Journal Title: Biochem Biophys Res Commun Volume: 424 Pages: 112-117
  • DOI: 10.1016/j.bbrc.2012.06.081
  • 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
  • Year and Date: 20130623-28
• [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
  • Year and Date: 20120605-09
• [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
  • Year and Date: 20110921-24
• [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