体外上皮气道模型揭示了EHF在肺稳态和疾病中的关键功能。

IF 3.3 3区 医学 Q2 CELL BIOLOGY
Disease Models & Mechanisms Pub Date : 2025-06-01 Epub Date: 2025-07-01 DOI:10.1242/dmm.052106
Laetitia Pinte, Marta Vila-Gonzalez, Eleanor C Williams, Erika Causa, Ricardo Fradique, Tekle Pauzaite, Charlotte Passemar, Silvia Becca, Christopher Gribben, Shiqi Ye, Maha Al-Thani, Fabian Bachinger, Floris J M Roos, James A Nathan, Irina Mohorianu, Andres Floto, Pietro Cicuta, Ludovic Vallier
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引用次数: 0

摘要

在肺气道中,多种类型的细胞促进气流进入肺泡,清除碎屑、颗粒和病原体。这些重要的过程在慢性炎症性呼吸道疾病中受到阻碍,其中上皮通常遭受炎症、感染和缺氧。越来越多的证据强调了修饰基因在对这些致病过程的反应和抗性中的关键作用。在这里,我们试图研究转录因子EHF,这是先前研究提出的一个假定的修饰基因,但其功能作用仍然不明确。为了探索这个问题,我们在人诱导的多能干细胞衍生的肺细胞中敲除EHF,并检查了随后的表型和功能影响。EHF缺失可增强囊性纤维化跨膜电导调节因子活性,导致基底细胞转录组改变,增加经上皮电阻,降低hif -1α-介导的缺氧反应。在这里,我们表明EHF表达的变化可以通过几种机制影响肺部疾病,从而突出了新疗法的前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An in vitro model of the epithelial airway reveals a key function for EHF in lung homeostasis and disease.

In the lung airways, multiple cell types facilitate airflow to alveoli, clearing out debris, particles and pathogens. These vital processes are impeded in chronic inflammatory respiratory diseases, in which the epithelium typically suffers from inflammation, infections and hypoxia. An increasing body of evidence highlights the critical role of modifier genes in responses and resistance against these pathogenic processes. Here, we sought to study the transcription factor EHF, suggested by previous studies as a putative modifier gene, yet its functional role remains ambiguous. To explore this question, we knocked out EHF in human induced pluripotent stem cell-derived lung cells and examined the subsequent phenotypic and functional impacts. Loss of EHF enhanced cystic fibrosis transmembrane conductance regulator activity, led to transcriptomic changes in basal cells, increased transepithelial electrical resistance and reduced HIF-1α-mediated response to hypoxia. Here, we show that variation in EHF expression can impact lung diseases through several mechanisms, thereby highlighting prospects for novel therapies.

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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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