Role of ion channels in the development of COPD

离子通道在 COPD 发展中的作用

基本信息

批准号：
8603277
负责人：
Estelle A Cormet-Boyaka
金额：
$ 17.74万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-07 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8603277
关键词：
Accounting Acute Affect Alleles Alveolar American Apical Basic Science Cause of Death Cells Chest Chloride Channels Chronic Chronic Bronchitis Chronic Obstructive Airway Disease Cigarette Smoker Clinical Research Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Data Development Disease Environmental Pollutants Epithelial Cells Exhibits Fluids and Secretions Functional disorder Gene Mutation Genes Homeostasis Human Hydration status Hyperplasia IL8 gene In Vitro Individual Inflammation Inflammatory Inflammatory Response Pathway Ion Channel Ions Knock-out Lead Link Liquid substance Lung Lung diseases Maintenance Mechanics Mediating Medical MicroRNAs Molecular Profiling Mucous body substance Mus Mutate Mutation Pathology Pathway interactions Patients Predisposition Prevention Production Protein C Inhibitor Proteins Pulmonary Emphysema Recruitment Activity Research Research Personnel Retrospective Studies Risk Role Sampling Smoking Smoking History Societies Surface Testing United States Wound Healing chemokine cigarette smoke-induced cigarette smoking cigarette smoking cost driving force in vivo innovation insight laser capture microdissection mRNA Expression macrophage mortality mouse model neutrophil novel novel marker prevent protein expression public health relevance pulmonary function response

项目摘要

DESCRIPTION (provided by applicant): Over 12 million Americans have chronic obstructive pulmonary disease (COPD). Although approximately 1 out of 5 cigarette smokers develop COPD, smoking accounts for 90% of development of COPD. We have evidence that the expression of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is suppressed in human samples from COPD patients and that cigarette smoke reduces the expression of CFTR in lung epithelial cells. CFTR is a chloride channel that is primarily expressed in epithelial cells where it regulates fluid homeostasis. Loss of CFTR function is associated with accumulation of mucus in the lung, abnormal inflammation and wound repair. Therefore, the potential importance of cigarette smoke-induced CFTR abnormalities in the pathophysiology of smoking-related diseases should be further evaluated. Over 10 million Americans are asymptomatic carriers of one CFTR mutation. This implicate that cigarette smoking will further decrease CFTR protein expression and might lead to increased risk of pulmonary diseases. This study will assess the contribution of CFTR to the development of COPD using a mouse model expressing reduced or no CFTR protein. This proposal will also identify the role of CFTR in lung responses to cigarette smoking. These studies will identify new markers that could be targeted for therapy.

描述（由申请人提供）：超过1200万美国人患有慢性阻塞性肺疾病（COPD）。尽管在5名吸烟者中，大约有1个发展COPD，但吸烟占COPD发展的90％。我们有证据表明，在COPD患者的人类样本中抑制了囊性纤维化跨膜电导调节剂（CFTR）的表达，并且香烟烟雾降低了肺上皮细胞中CFTR的表达。 CFTR是一种氯化物通道，主要在调节流体稳态的上皮细胞中表达。 CFTR功能的丧失与肺部粘液的积累有关，异常炎症和伤口修复。因此，应进一步评估香烟烟雾引起的CFTR异常在与吸烟有关的疾病的病理生理学中的潜在重要性。超过1000万美国人是一个CFTR突变的无症状携带者。这意味着吸烟将进一步降低CFTR蛋白表达，并可能导致肺部疾病的风险增加。这项研究将使用表达降低或没有CFTR蛋白的小鼠模型来评估CFTR对COPD发展的贡献。该建议还将确定CFTR在肺对吸烟的反应中的作用。这些研究将确定可以针对治疗的新标记。