Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
Respir Res. 2019 Sep 2;20(1):200. doi: 10.1186/s12931-019-1170-3.
Chronic Obstructive Pulmonary Disease (COPD) is a complex disease resulting in respiratory failure and represents the third leading cause of global death. The two classical phenotypes of COPD are chronic bronchitis and emphysema. Owing to similarities between chronic bronchitis and the autosomal-recessive disease Cystic Fibrosis (CF), a significant body of research addresses the hypothesis that dysfunctional CF Transmembrane Conductance Regulator (CFTR) is implicated in the pathogenesis of COPD. Much less attention has been given to emphysema in this context, despite similarities between the two diseases. These include early-onset cellular senescence, similar comorbidities, and the finding that CF patients develop emphysema as they age. To determine a potential role for CFTR dysfunction in the development of emphysema, Cftr (Wild-type; WT), Cftr (heterozygous), and Cftr (knock-out; KO) mice were aged or exposed to cigarette smoke and analyzed for airspace enlargement. Aged knockout mice demonstrated increased alveolar size compared to age-matched wild-type and heterozygous mice. Furthermore, both heterozygous and knockout mice developed enlarged alveoli compared to their wild-type counterparts following chronic smoke exposure. Taken into consideration with previous findings that cigarette smoke leads to reduced CFTR function, our findings suggest that decreased CFTR expression sensitizes the lung to the effects of cigarette smoke. These findings may caution normally asymptomatic CF carriers against exposure to cigarette smoke; as well as highlight emphysema as a future challenge for CF patients as they continue to live longer. More broadly, our data, along with clinical findings, may implicate CFTR dysfunction in a pathology resembling accelerated aging.
慢性阻塞性肺疾病（COPD）是一种复杂的疾病，导致呼吸衰竭，是全球死亡的第三大主要原因。COPD 的两种经典表型是慢性支气管炎和肺气肿。由于慢性支气管炎与常染色体隐性遗传疾病囊性纤维化（CF）之间存在相似性，大量研究都在探讨 CF 跨膜电导调节蛋白（CFTR）功能障碍是否与 COPD 的发病机制有关。然而，在这种情况下，人们对肺气肿的关注要少得多，尽管这两种疾病存在相似之处。这些相似之处包括细胞衰老的早发、相似的合并症，以及 CF 患者随着年龄的增长会发展为肺气肿的发现。为了确定 CFTR 功能障碍在肺气肿发展中的潜在作用，对 Cftr（野生型；WT）、Cftr（杂合型）和 Cftr（敲除型；KO）小鼠进行了增龄或香烟烟雾暴露，并对其进行了气腔扩大分析。与年龄匹配的野生型和杂合型小鼠相比，增龄的 KO 小鼠表现出更大的肺泡大小。此外，与野生型小鼠相比，香烟烟雾暴露后，杂合型和 KO 型小鼠的肺泡也会增大。结合先前的研究结果，即香烟烟雾会导致 CFTR 功能下降，我们的研究结果表明 CFTR 表达的减少会使肺部对香烟烟雾的影响更加敏感。这些发现可能会警告通常无症状的 CF 携带者避免接触香烟烟雾；并强调肺气肿作为 CF 患者随着寿命延长而面临的未来挑战。更广泛地说，我们的数据以及临床发现可能表明 CFTR 功能障碍与类似加速衰老的病理学有关。
