慢性阻塞性肺疾病（COPD）是一种无法有效减少死亡率或减缓疾病进展的致残性肺疾病。COPD是全球第三大死亡原因，其特点是由于慢性支气管炎和肺泡损伤/肺气肿引起的气流限制。长期吸烟暴露（CS）会损伤气道和肺泡上皮，并仍然是COPD发病机制的主要风险因素。我们发现，肺气道上皮细胞（AECs）以及慢性阻塞性肺疾病患者或CS诱导肺损伤的野生型小鼠的II型肺泡上皮（AT2）细胞中，穴居膜蛋白1（caveolin-1 ）、抑癌蛋白p53和纤溶酶原激活抑制剂-1（PAI-1），即p53的下游靶点之一的表达明显增加。此外，p53及PAI-1缺失的小鼠对CS诱导的肺损伤具有抵抗性。此外，处理来自COPD患者或病毒型小鼠经CS诱导的肺损伤（CS-LI）的AEC、AT2细胞或肺组织切片，使用一个七氨基酸穴居膜蛋白1支架结构域肽（CSP7），可以减少AEC的粘液分泌并提高AT2细胞的存活能力。值得注意的是，通过增加穴居膜蛋白1和p53来诱导PAI-1表达，对AEC的黏液细胞化生和粘液分泌，以及AT2细胞的减少活力起到了贡献作用，因为这会增加细胞衰老和凋亡，而CSP7可以消除这种影响。此外，将CS-LI的野生型小鼠用腹腔注射或气管雾化进行CSP7处理，可以减轻粘液分泌过多、肺泡损伤，并显着改善肺功能。本研究验证了CSP7在CS-LI和COPD治疗中的潜在治疗作用。

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease with no effective treatment that can reduce mortality or slow the disease progression. COPD is the third leading cause of global death and is characterized by airflow limitations due to chronic bronchitis and alveolar damage/emphysema. Chronic cigarette smoke exposure (CS) damages airway and alveolar epithelium and remains a major risk factor for the pathogenesis of COPD. We found that the expression of caveolin-1, tumor suppressor protein; p53, and plasminogen activator inhibitor-1 (PAI-1), one of the downstream targets of p53, were markedly increased in airway epithelial cells (AECs) as well as in type II alveolar epithelial (AT2) cells from the lungs of patients with COPD or wild-type mice with CS-induced lung injury (CS-LI). Moreover, p53- and PAI-1-deficient mice resisted CS-LI. Furthermore, treatment of AECs, AT2 cells or lung tissue slices from patients with COPD, or mice with CS-LI with a seven amino acid caveolin-1 scaffolding domain peptide (CSP7) reduced mucus hypersecretion in AECs and improved AT2 cell viability. Notably, induction of PAI-1 expression via increased caveolin-1 and p53 contributed to mucous cell metaplasia and mucus hypersecretion in AECs, and reduced AT2 viability, due to increased senescence and apoptosis, which was abrogated by CSP7. In addition, treatment of wild-type mice having CS-LI with CSP7 by intraperitoneal injection or nebulization via airways attenuated mucus hypersecretion, alveolar injury, and significantly improved lung function. This study validates the potential therapeutic role of CSP7 for treating CS-LI and COPD.