Ancel Julien, Belgacemi Randa, Diabasana Zania, Perotin Jeanne-Marie, Bonnomet Arnaud, Dewolf Maxime, Launois Claire, Mulette Pauline, Deslée Gaëtan, Polette Myriam, Dormoy Valérian
Inserm UMR-S1250, P3Cell, Université de Reims Champagne Ardenne, SFR CAP-SANTE, 51092 Reims, France.
Department of Respiratory Diseases, Centre Hospitalier Universitaire de Reims, Hôpital Maison Blanche, 51092 Reims, France.
Diagnostics (Basel). 2021 Aug 31;11(9):1579. doi: 10.3390/diagnostics11091579.
Chronic obstructive pulmonary disease (COPD) is a frequent respiratory disease. However, its pathophysiology remains partially elucidated. Epithelial remodeling including alteration of the cilium is a major hallmark of COPD, but specific assessments of the cilium have been rarely investigated as a diagnostic tool in COPD. Here we explore the dysregulation of the ciliary function (ciliary beat frequency (CBF)) and differentiation (multiciliated cells formation in air-liquid interface cultures) of bronchial epithelial cells from COPD ( = 17) and non-COPD patients ( = 15). CBF was decreased by 30% in COPD (11.15 +/- 3.37 Hz vs. 7.89 +/- 3.39 Hz, = 0.037). Ciliary differentiation was altered during airway epithelial cell differentiation from COPD patients. While the number of multiciliated cells decreased ( < 0.005), the number of primary ciliated cells increased ( < 0.05) and primary cilia were shorter ( < 0.05). Altogether, we demonstrate that COPD can be considered as a ciliopathy through both primary non-motile cilia modifications (related to airway epithelial cell repair and remodeling) and motile cilia function impairment (associated with decrease sputum clearance and clinical respiratory symptoms). These observations encourage considering cilia-associated features in the complex COPD physiopathology and highlight the potential of cilia-derived biomarkers for diagnosis.
慢性阻塞性肺疾病(COPD)是一种常见的呼吸系统疾病。然而,其病理生理学仍部分有待阐明。包括纤毛改变在内的上皮重塑是COPD的一个主要标志,但作为COPD诊断工具的纤毛特异性评估很少被研究。在此,我们探讨了COPD患者(n = 17)和非COPD患者(n = 15)支气管上皮细胞的纤毛功能失调(纤毛摆动频率(CBF))和分化(气液界面培养中的多纤毛细胞形成)情况。COPD患者的CBF降低了30%(11.15±3.37Hz对7.89±3.39Hz,P = 0.037)。COPD患者气道上皮细胞分化过程中的纤毛分化发生改变。多纤毛细胞数量减少(P < 0.005),而原发性纤毛细胞数量增加(P < 0.05),且原发性纤毛更短(P < 0.05)。总之,我们证明COPD可通过原发性非运动性纤毛改变(与气道上皮细胞修复和重塑有关)和运动性纤毛功能受损(与痰液清除减少和临床呼吸道症状相关)被视为一种纤毛病。这些观察结果促使人们在复杂的COPD病理生理学中考虑与纤毛相关的特征,并突出了纤毛衍生生物标志物在诊断方面的潜力。