CFTR expression regulation by the unfolded protein response.
CFTR expression regulation by the unfolded protein response.
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CFTR 表达由未折叠蛋白反应调节。
DOI：
10.1016/b978-0-12-385928-0.00001-8
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发表时间：
2011
影响因子：
--
通讯作者：
Bebok, Zsuzsa
中科院分区：
文献类型：
--
作者：
Bartoszewski, Rafal;Rab, Andras;Fu, Lianwu;Bartoszewska, Sylwia;Collawn, James;Bebok, Zsuzsa
囊性纤维化跨膜传导调节因子（CFTR）是一种氯离子通道，是上皮功能的关键调节因子。CFTR基因突变导致CFTR蛋白减少或功能障碍，并引起囊性纤维化（CF），一种影响多个器官的全身性外分泌病。在气道中，CFTR功能的丧失导致粘液增厚、粘膜纤毛清除减少、慢性感染和呼吸衰竭。常见的气道疾病，如支气管炎和慢性阻塞性肺病（COPD）也存在CF样症状，如粘液充血和慢性炎症，而CFTR没有突变。COPD和慢性支气管炎的主要风险因素包括环境压力损伤，例如污染物和感染，这些通常会导致缺氧状况。此外，环境因素，如香烟烟雾和活性氧物质已被牵连在减少CFTR功能。这些因素对细胞应激反应的激活促进了差异性的、应激相关的基因表达调节。在我们对CFTR表达调控机制的研究中，我们已经表明，ER应激反应，未折叠蛋白反应（UPR），在转录，翻译和成熟水平上降低CFTR表达。在这里，我们提供了一个详细的描述，我们采用的方法来研究CFTR表达调控的UPR。类似的方法也适用于其他基因的研究，以及它们如何受到普遍定期审议的影响。
The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel and key regulator of epithelial functions. Mutations in the CFTR gene lead to reduced or dysfunctional CFTR protein and cause cystic fibrosis (CF), a generalized exocrinopathy affecting multiple organs. In the airways, loss of CFTR function leads to thickened mucus, reduced mucociliary clearance, chronic infections, and respiratory failure. Common airway disorders such as bronchitis and chronic obstructive pulmonary disease (COPD) also present CF-like symptoms such as mucus congestion and chronic inflammation without mutations in CFTR. The primary risk factors for COPD and chronic bronchitis include environmental stress insults such as pollutants and infections that often result in hypoxic conditions. Furthermore, environmental factors such as cigarette smoke and reactive oxygen species have been implicated in reduced CFTR function. Activation of cellular stress responses by these factors promotes differential, stress-associated gene expression regulation. During our investigations on the mechanisms of CFTR expression regulation, we have shown that the ER stress response, the unfolded protein response (UPR), decreases CFTR expression at the transcriptional, translational, and maturational levels. Here, we provide a detailed description of the methods we employ to study CFTR expression regulation by the UPR. Similar approaches are applicable in studies on other genes and how they are affected by the UPR.