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

FUT8在慢性阻塞性肺疾病发展中的作用

• 批准号: 23591118
• 负责人: GAO CONGXIAO
• 金额: $ 3.33万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591118/
• 关键词: 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

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.

使用暴露于香烟烟雾的Fut 8杂合基因敲除小鼠研究核心岩藻糖基化在COPD发病机制中的生理相关性。在暴露的早期阶段，观察到FUT 8活性显著降低和基质金属蛋白酶（MMP）-9活性升高。肺气肿只在野生型小鼠所需暴露期的一半内发生。TGF-β 1-Smad 2信号通路已丧失功能。此外，我们的研究表明，在有症状的稳定期COPD患者或高危门诊患者（n=226）中，1秒用力呼气量（FEV 1）的年下降速度更快与FUT 8活性降低显著相关。FUT 8活性较低的患者发生急性加重的频率更高。这些数据表明，FUT 8活性降低与COPD进展相关，血清FUT 8活性是COPD进展和加重的微创预测生物标志物。

项目成果

Sensitivity of heterozygous α1, 6 fucosyltransferase knock out mice to cigarette smoke-induced emphysema : implication of aberrant TGF-β signaling and MMP gene expression

杂合 α1, 6 岩藻糖基转移酶敲除小鼠对香烟烟雾诱发的肺气肿的敏感性：异常 TGF-β 信号传导和 MMP 基因表达的影响

• 发表时间: 2012
• 期刊: J. Biol. Chem
• 作者: Gao;C.;Shirato;K.;Taniguchi;N.;et al.(他10名、7番目)
• 通讯作者: et al.(他10名、7番目)

alpha1,6Fucosyltransferase (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)

α1,6岩藻糖基转移酶 (Fut8) 与小鼠吸烟诱发肺气肿的易感性有关，并且可能是人类慢性阻塞性肺病 (COPD) 的非侵入性预测标记

• 发表时间: 2012
• 作者: Sakuma M;Morimoto T;Kubota Y;Seki S;Takada K;Hiraide A;HIROSHI KIYONO;Naoyuki Taniguchi
• 通讯作者: Naoyuki Taniguchi

Biological functions of branched N-glycans related to physiology and pathology of extracellular matrix.Extracellular Matrix: Pathobiology and Signaling

支链 N-聚糖的生物学功能与细胞外基质的生理学和病理学相关。细胞外基质：病理生物学和信号转导

• 发表时间: 2012
• 作者: Gao C;Ohtsubo K;Gu J;and Taniguchi N
• 通讯作者: and Taniguchi N

Sensitivity of heterozygous a1, 6-fucosyltransferase knock out mice to cigarette smoke-induced emphysema : Implication of aberrant TGF-βsignaling and MMP gene expression

杂合 a1, 6-岩藻糖基转移酶敲除小鼠对香烟烟雾诱发的肺气肿的敏感性：异常 TGF-β 信号传导和 MMP 基因表达的影响

• 发表时间: 2012
• 作者: Gao;C.
• 通讯作者: C.

Molecular mechanism of the high susceptibility of alpha 1,6 fucosyltransferase (Fut8) heterozygous knockout mice to cigarette smoke-induced emphysema

α1,6岩藻糖基转移酶（Fut8）杂合基因敲除小鼠吸烟诱发肺气肿高易感性的分子机制

• 发表时间: 2011
• 作者: Gao;C.
• 通讯作者: C.