New asthma biomarkers: lessons from murine models of acute and chronic asthma
New asthma biomarkers: lessons from murine models of acute and chronic asthma
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DOI：
10.1152/ajplung.90367.2008
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发表时间：
2009-02-01
影响因子：
4.9
通讯作者：
Cataldo, Didier
中科院分区：
文献类型：
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作者：
Di Valentin, Emmanuel;Crahay, Celine;Cataldo, Didier
陈建军，陈建军，陈建军，陈建军，陈建军，陈建军，陈建军，陈建军，陈建军，陈建军，陈建军。[J] .中国生物医学工程学报，2009,31(6):557 - 557。首次发表于2008年11月21日；doi: 10.1152 / ajplung.90367.2008。-许多哮喘患者目前的治疗方法无法完全控制，其中一些患者表现出气道重塑，导致肺功能严重下降。本研究的目的是揭示哮喘的新介质，以更好地了解病理生理，提出或验证新的潜在治疗靶点。一个模拟急性或慢性哮喘疾病的哮喘小鼠模型被用来选择在急性和慢性疾病中经历调节的基因。小鼠暴露于卵清蛋白或PBS中1,5,10周[短期，中期和长期模型（ST， IT和LT）]，使用Affymetrix 430 2.0全基因组微阵列研究肺中的基因表达，并进一步通过RT-PCR和免疫组织化学对选定的靶点进行确认。我们报道在ST、IT和LT中分别有598、1406和117个基因上调，490、153和321个基因下调。在过敏原暴露过程中，与粘膜分泌相关的基因表达逐渐扩增，而与生长和分化因子、基质金属蛋白酶和胶原蛋白相关的基因则主要在IT时上调。相比之下，与细胞分裂相关的基因在ST和IT期上调，而在lt期下调。在本研究中，除了证实Arg1、Slc26a4、Ear11和Mmp12基因在整个哮喘病理过程中高度调节外，我们首次发现Agr2、Scin和Cd209e基因在整个过敏原暴露过程中过度表达，因此可能被认为是治疗哮喘的合适的新潜在靶点。
Di Valentin E, Crahay C, Garbacki N, Hennuy B, Gueders M, Noel A, Foidart JM, Grooten J, Colige A, Piette J, Cataldo D. New asthma biomarkers: lessons from murine models of acute and chronic asthma. Am J Physiol Lung Cell Mol Physiol 296: L185-L197, 2009. First published November 21, 2008; doi:10.1152/ajplung.90367.2008.-Many patients suffering from asthma are not fully controlled by currently available treatments, and some of them display an airway remodeling leading to exaggerated lung function decline. The aim of the present study was to unveil new mediators in asthma to better understand pathophysiology and propose or validate new potential therapeutic targets. A mouse model of asthma mimicking acute or chronic asthma disease was used to select genes undergoing a modulation in both acute and chronic conditions. Mice were exposed to ovalbumin or PBS for 1, 5, and 10 wk [short-, intermediate-, and long-term model (ST, IT, and LT)], and gene expression in the lung was studied using an Affymetrix 430 2.0 genome-wide microarray and further confirmed by RT-PCR and immunohistochemistry for selected targets. We report that 598, 1,406, and 117 genes were upregulated and 490, 153, 321 downregulated at ST, IT, and LT, respectively. Genes related to mucous secretion displayed a progressively amplified expression during the allergen exposure protocol, whereas genes corresponding to growth and differentiation factors, matrix metalloproteinases, and collagens were mainly upregulated at IT. By contrast, genes related to cell division were upregulated at ST and IT and were downregulated at LT. In this study, besides confirming that Arg1, Slc26a4, Ear11, and Mmp12 genes are highly modulated throughout the asthma pathology, we show for the first time that Agr2, Scin, and Cd209e genes are overexpressed throughout the allergen exposure and might therefore be considered as suitable new potential targets for the treatment of asthma.