The role of CLCA proteins in inflammatory airway disease.

The role of CLCA proteins in inflammatory airway disease.
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DOI:
10.1146/annurev.physiol.010908.163253
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发表时间:
2009
影响因子:
18.2
通讯作者:
Holtzman MJ
Holtzman MJ
中科院分区:
医学1区
文献类型:
--
作者:
Patel AC;Brett TJ;Holtzman MJ

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炎症性气道疾病,如哮喘和慢性阻塞性肺疾病(COPD),在每个人身上表现出不同的刻板特征。在慢性肺部疾病的实验性小鼠模型中,这些个体疾病特征可以遗传分离,从而与不同的决定因素相关联。功能基因组分析表明,这些特征中至少有一种,即粘膜细胞化生,取决于钙活化氯离子通道(CLCA)基因家族的成员。在这里,我们回顾了CLCA家族生物化学的进展,以及CLCA家族成员在实验模型和人类中粘液细胞化生和可能的气道高反应性发展中的作用的证据。基于这些信息,我们建立了CLCA蛋白不是具有离子通道功能的完整膜蛋白的模型,而是在健康和疾病条件下特异性调节气道靶细胞的分泌信号分子。
Inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) exhibit stereotyped traits that are variably expressed in each person. In experimental mouse models of chronic lung disease, these individual disease traits can be genetically segregated and thereby linked to distinct determinants. Functional genomic analysis indicates that at least one of these traits, mucous cell metaplasia, depends on members of the calcium-activated chloride channel (CLCA) gene family. Here we review advances in the biochemistry of the CLCA family and the evidence of a role for CLCA family members in the development of mucous cell metaplasia and possibly airway hyperreactivity in experimental models and in humans. Based on this information, we develop the model that CLCA proteins are not integral membrane proteins with ion channel function, but instead are secreted signaling molecules that specifically regulate airway target cells in healthy and disease conditions.
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