Overexpression of chitinase 3-like 1/YKL-40 in lung-specific IL-18-transgenic mice, smokers and COPD.
Overexpression of chitinase 3-like 1/YKL-40 in lung-specific IL-18-transgenic mice, smokers and COPD.
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DOI：
10.1371/journal.pone.0024177
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Aizawa H
中科院分区：
文献类型：
--
作者：
Sakazaki Y;Hoshino T;Takei S;Sawada M;Oda H;Takenaka S;Imaoka H;Matsunaga K;Ota T;Abe Y;Miki I;Fujimoto K;Kawayama T;Kato S;Aizawa H
我们分析了使用肺特异性IL-18转基因小鼠开发的COPD小鼠模型的肺mRNA表达谱。在该转基因小鼠中，发现608个基因的表达与对照WT小鼠相比变化超过2倍，并被聚类为4组。140个基因的表达在各年龄段均呈组成性增加，215个基因随增龄逐渐增加，171个基因随增龄逐渐减少，82个基因在9周龄时暂时减少。有趣的是，几丁质酶相关基因几丁质酶3样1（Chi 3l 1），Chi 3l 3和酸性哺乳动物几丁质酶（AMCase）的mRNA水平在转基因小鼠的肺中显着高于对照小鼠。IL-18转基因小鼠的肺和血清中Chi 3l 1蛋白水平随着年龄的增长而显著增加，而WT小鼠则没有。以前的研究表明Chi 3l 3和AMCase是IL-13驱动的几丁质酶样蛋白。然而，IL-13基因缺失并没有降低IL-18转基因小鼠肺中Chi 3l 1蛋白的水平。基于我们的小鼠模型基因表达数据，我们分析了吸烟者和COPD患者血清中YKL-40（Chi 3l 1的人类同源物）的蛋白水平。16例COPD患者接受了高分辨率计算机断层扫描（HRCT）检查。通过使用截止值为−950 Hounsfield单位的密度掩模来评估肺气肿，以计算低衰减面积百分比（LAA%）。我们在28名吸烟者和45名COPD患者的样本中观察到显著高于30名非吸烟者的血清水平。COPD患者血清YKL-40水平与%FEV1呈显著负相关。COPD患者血清YKL-40水平与LAA%呈显著正相关。因此，我们的研究结果表明，几丁质酶相关基因可能在建立吸烟者和COPD患者的肺部炎症和肺气肿的变化中发挥重要作用。
We analyzed the lung mRNA expression profiles of a murine model of COPD developed using a lung-specific IL-18-transgenic mouse. In this transgenic mouse, the expression of 608 genes was found to vary more than 2-fold in comparison with control WT mice, and was clustered into 4 groups. The expression of 140 genes was constitutively increased at all ages, 215 genes increased gradually with aging, 171 genes decreased gradually with aging, and 82 genes decreased temporarily at 9 weeks of age. Interestingly, the levels of mRNA for the chitinase-related genes chitinase 3-like 1 (Chi3l1), Chi3l3, and acidic mammalian chitinase (AMCase) were significantly higher in the lungs of transgenic mice than in control mice. The level of Chi3l1 protein increased significantly with aging in the lungs and sera of IL-18 transgenic, but not WT mice. Previous studies have suggested Chi3l3 and AMCase are IL-13-driven chitinase-like proteins. However, IL-13 gene deletion did not reduce the level of Chi3l1 protein in the lungs of IL-18 transgenic mice. Based on our murine model gene expression data, we analyzed the protein level of YKL-40, the human homolog of Chi3l1, in sera of smokers and COPD patients. Sixteen COPD patients had undergone high resolution computed tomography (HRCT) examination. Emphysema was assessed by using a density mask with a cutoff of −950 Hounsfield units to calculate the low-attenuation area percentage (LAA%). We observed significantly higher serum levels in samples from 28 smokers and 45 COPD patients compared to 30 non-smokers. In COPD patients, there was a significant negative correlation between serum level of YKL-40 and %FEV1. Moreover, there was a significant positive correlation between the serum levels of YKL-40 and LAA% in COPD patients. Thus our results suggest that chitinase-related genes may play an important role in establishing pulmonary inflammation and emphysematous changes in smokers and COPD patients.
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DOI：
10.1165/rcmb.2003-0306oc
发表时间：
2004-12-01
影响因子：
6.4
作者：
Kitasato, Y;Hoshino, T;Aizawa, H
通讯作者：
Aizawa, H
影响因子：
4.4
作者：
Hoshino, T;Kawase, Y;Oizumi, K
通讯作者：
Oizumi, K
DOI：
10.1165/rcmb.2008-0182oc
发表时间：
2009-12
影响因子：
6.4
作者：
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DOI：
10.1084/jem.20081271
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lee CG;Hartl D;Lee GR;Koller B;Matsuura H;Da Silva CA;Sohn MH;Cohn L;Homer RJ;Kozhich AA;Humbles A;Kearley J;Coyle A;Chupp G;Reed J;Flavell RA;Elias JA
通讯作者：
Elias JA
影响因子：
158.5
作者：
Chupp, Geoffrey L.;Lee, Chun Geun;Elias, Jack A.
通讯作者：
Elias, Jack A.