Petit Laure M G, Belgacemi Randa, Mulette Pauline, Brisebarre Audrey, Saber Cherif Lynda, Devilliers Maëva A, Hatoum Sarah, Ancel Julien, Delepine Gonzague, Durlach Anne, Polette Myriam, Deslée Gaëtan, Perotin Jeanne-Marie, Dormoy Valérian
Université de Reims Champagne-Ardenne, INSERM, P3Cell UMR-S1250, Reims, France.
Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA, United States.
Front Cell Dev Biol. 2025 Jul 2;13:1566251. doi: 10.3389/fcell.2025.1566251. eCollection 2025.
Airway epithelium remodeling is a hallmark of chronic obstructive pulmonary disease (COPD) pathogenesis. Hedgehog signaling is activated during airway epithelial repair to warrant proliferation and during cell differentiation to establish a fully functional epithelium with optimal mucociliary clearance. Consequently, it was found to be altered in COPD patients. Using transcriptomic analysis on air-liquid interface airway epithelial cells during differentiation upon Hedgehog pathway inhibition, we highlighted potential regulators of COPD-associated epithelial remodeling. Furthermore, the alteration of POU5F1 (OCT3/4) was validated in COPD airway epithelial cells and lung tissues. Although further investigations are required, these findings uncovered essential clues tethering respiratory epithelial cell plasticity and Hedgehog signaling.
气道上皮重塑是慢性阻塞性肺疾病(COPD)发病机制的一个标志。在气道上皮修复过程中,刺猬信号通路被激活以保证细胞增殖,在细胞分化过程中被激活以建立具有最佳黏液纤毛清除功能的完全功能性上皮。因此,发现该通路在COPD患者中发生了改变。通过对刺猬信号通路抑制后分化过程中的气液界面气道上皮细胞进行转录组分析,我们突出了COPD相关上皮重塑的潜在调节因子。此外,POU5F1(OCT3/4)的改变在COPD气道上皮细胞和肺组织中得到了验证。尽管还需要进一步研究,但这些发现揭示了连接呼吸道上皮细胞可塑性和刺猬信号通路的重要线索。