Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation, small airway remodeling, and emphysema. Airway remodeling in patients with COPD involves both the airway epithelium and the subepithelial extracellular matrix (ECM). However, it is currently unknown how epithelial remodeling in COPD airways depends on the relative influence from inherent defects in the epithelial cells and alterations in the ECM. To address this, we analyzed global gene expression in COPD human bronchial epithelial cells (HBEC) and normal HBEC after repopulation on decellularized bronchial scaffolds derived from patients with COPD or donors without COPD. COPD HBEC grown on bronchial scaffolds showed an impaired ability to initiate ciliated-cell differentiation, which was evident on all scaffolds regardless of their origin. In addition, although normal HBEC were less affected by the disease state of the bronchial scaffolds, COPD HBEC showed a gene expression pattern indicating increased proliferation and a retained basal-cell phenotype when grown on COPD bronchial scaffolds compared with normal bronchial scaffolds. By using mass spectrometry, we identified 13 matrisome proteins as being differentially abundant between COPD bronchial scaffolds and normal bronchial scaffolds. These observations are consistent with COPD pathology and suggest that both epithelial cells and the ECM contribute to epithelial-cell remodeling in COPD airways.

慢性阻塞性肺疾病 (COPD) 的特征是气道炎症、小气道重塑和肺气肿。COPD 患者的气道重塑涉及气道上皮和上皮下细胞外基质 (ECM)。然而，目前尚不清楚 COPD 气道中的上皮重塑如何取决于上皮细胞固有缺陷和 ECM 改变的相对影响。为了解决这个问题，我们分析了 COPD 人支气管上皮细胞 (HBEC) 和正常 HBEC 在来自 COPD 患者或非 COPD 供体的脱细胞支气管支架上重新填充后的全局基因表达。在支气管支架上生长的 COPD HBEC 显示出启动纤毛细胞分化的能力受损，这在所有支架上都很明显，无论其来源如何。此外，尽管正常 HBEC 受支气管支架疾病状态的影响较小，但与正常支气管支架相比，COPD HBEC 显示出一种基因表达模式，表明在 COPD 支气管支架上生长时增殖增加并保留基底细胞表型。通过使用质谱法，我们确定了 13 种基质蛋白在 COPD 支气管支架和正常支气管支架之间差异丰富。这些观察结果与 COPD 病理学一致，并表明上皮细胞和 ECM 都有助于 COPD 气道中的上皮细胞重塑。COPD HBEC 显示出基因表达模式，表明与正常支气管支架相比，在 COPD 支气管支架上生长时增殖增加并保留基底细胞表型。通过使用质谱法，我们确定了 13 种基质蛋白在 COPD 支气管支架和正常支气管支架之间差异丰富。这些观察结果与 COPD 病理学一致，并表明上皮细胞和 ECM 都有助于 COPD 气道中的上皮细胞重塑。COPD HBEC 显示出基因表达模式，表明与正常支气管支架相比，在 COPD 支气管支架上生长时增殖增加并保留基底细胞表型。通过使用质谱法，我们确定了 13 种基质蛋白在 COPD 支气管支架和正常支气管支架之间差异丰富。这些观察结果与 COPD 病理学一致，并表明上皮细胞和 ECM 都有助于 COPD 气道中的上皮细胞重塑。