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POU5F1在慢性阻塞性肺疾病中介导刺猬信号通路与上皮重塑。

POU5F1 bridges Hedgehog signaling and epithelial remodeling in COPD.

作者信息

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

机构信息

Université de Reims Champagne-Ardenne, INSERM, P3Cell UMR-S1250, Reims, France.

Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA, United States.

出版信息

Front Cell Dev Biol. 2025 Jul 2;13:1566251. doi: 10.3389/fcell.2025.1566251. eCollection 2025.

DOI:10.3389/fcell.2025.1566251
PMID:40673278
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12263618/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aeaa/12263618/e0650c6f33fe/fcell-13-1566251-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aeaa/12263618/3f50f8712308/fcell-13-1566251-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aeaa/12263618/e0650c6f33fe/fcell-13-1566251-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aeaa/12263618/3f50f8712308/fcell-13-1566251-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aeaa/12263618/e0650c6f33fe/fcell-13-1566251-g002.jpg

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本文引用的文献

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Identification of a distal enhancer regulating hedgehog interacting protein gene in human lung epithelial cells.鉴定人肺上皮细胞中 Hedgehog 相互作用蛋白基因的远端增强子。
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Primary ciliogenesis is a crucial step for multiciliated cell determinism in the respiratory epithelium.初级纤毛发生是呼吸道上皮细胞多纤毛决定的关键步骤。
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Respir Res. 2021 Feb 27;22(1):74. doi: 10.1186/s12931-021-01665-4.
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Sonic hedgehog signalling as a potential endobronchial biomarker in COPD.声波刺猬因子信号通路作为慢性阻塞性肺疾病潜在的支气管内生物标志物
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