Evidence map›Paper›PMID 41622346›Full record

ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2026

Neutrophil extracellular traps induce airway epithelial-mesenchymal transition in a neutrophil-dominant asthmatic murine model through Hedgehog/Gli1 pathway.

Mengling Xia, Qing Wang, Yixia Jiang, Shan Lu, Fei Xu, Yinan Yao, Yuekang Li, Linying Wu, Jianya Zhou, Jianying Zhou

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Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Mengling XiaDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou, 310003, China.
Qing WangDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou, 310003, China.
Yixia JiangZhejiang University, No. 866 Yuhangtang Road, Hangzhou, 310058, China.
Shan LuDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou, 310003, China.
Fei XuDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou, 310003, China.
Yinan YaoDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou, 310003, China.
Yuekang LiDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou, 310003, China.
Linying WuDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou, 310003, China.
Jianya ZhouDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou, 310003, China. zhoujy@zju.edu.cn.
Jianying ZhouDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou, 310003, China. zjyhz@zju.edu.cn.

Funding

Basic Public Welfare Research Program of Zhejiang Province LTGY23H160021Key R&D Program of Zhejiang Provincial 2024C03187Key R&D Program of Zhejiang Provincial No.2023C03069the Youth Innovation Project of Zhejiang Provincial Medical and Health Science and Technology Program No.2023RC017Zhejiang Provincial Clinical Research Center for Respiratory Disease No.2022E50005
6 · The paper itself

Abstract

backgroundNeutrophilic asthma is one of the main types of severe asthma. Our previous studies demonstrated that neutrophil extracellular traps (NETs) contribute to its pathological process. However, the underlying mechanisms remains unclear. This study aimed to investigate the potential mechanisms of NETs in neutrophilic asthma.

methodsClinical samples were collected from patients with neutrophilic asthma and healthy controls. A neutrophil-dominant asthmatic murine model was established using ovalbumin (OVA), Freund's complete adjuvant (CFA) and lipopolysaccharide (LPS). Airway inflammation and remodeling were assessed by pathological staining. The expression of EMT markers and Hedgehog (Hh)/Gli1 pathway markers were measured by Western blot, qPCR, and immunofluorescence.

resultsWe found that the expression of dsDNA, one of the skeleton components of NETs, was significantly higher in the peripheral plasma of patients with neutrophilic asthma than that of healthy controls, and neutrophils in neutrophilic asthma patients were more likely to induce the production of NETs. We further demonstrated that NETs induced EMT in airway epithelial cells. Both in vivo and in vitro, we confirmed that reducing NETs formation or enhancing NETs degradation reversed EMT process, attenuated airway hyperresponsiveness (AHR) and alleviated airway inflammation in neutrophil-dominant asthmatic mouse model. We also found that the Hh/Gli1 pathway was activated during this process, and inhibition of the Hh/Gli1 pathway also reversed the EMT process of airway epithelium. Similarly, AHR and airway inflammation in neutrophil-dominant asthmatic mice were reduced.

conclusionsWe confirmed that NETs promote EMT in airway epithelium via activation the Hh/Gli1 signaling pathway, thus playing an important role in the pathogenesis of neutrophilic asthma. Targeting NETs or the Hh/Gli1 pathway may provide a promising therapeutic strategy for the treatment of severe neutrophilic asthma.

Indexed as

AsthmaEpithelial-Mesenchymal TransitionExtracellular TrapsHedgehog ProteinsNeutrophilsZinc Finger Protein GLI1AdultAnimalsDisease Models, AnimalDNAFemaleHumansLipopolysaccharidesLungMaleMiceDNAGLI1 protein, humanGli1 protein, mouseHedgehog ProteinsLipopolysaccharidesOvalbuminZinc Finger Protein GLI1Airway epitheliumAsthmaEpithelial-mesenchymal transitionHedgehog/Gli1 pathwayNeutrophil extracellular traps

Identifiers

PMID41622346

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.