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Background <p>Asthma is a prevalent chronic respiratory disease that affects lots of people all over the world. Characterized by multiple complex mechanisms, asthma poses substantial challenges for both patients and healthcare providers in clinical management. Comprehending the underlying mechanisms that drive the onset and progression of asthma is crucial for developing effective therapies.</p> Methods <p>The expression of CPA3 was analyzed via bioinformatics, and bulk RNA-seq datasets were utilized for this purpose. The findings were validated using quantitative real-time PCR and western blotting. A house dust mite–induced asthma mouse model was established to evaluate CPA3 expression in airway epithelial cells. Furthermore, the BEAS-2B cell line was used to investigate the potential mechanisms by which CPA3 contributes to the pathogenesis and progression of asthma.</p> Results <p>We identified four key genes from DEGs and module genes from WGCNA based on RNA-seq data of asthma. Applying random forest algorithm, we focus on CPA3 as the most significant gene in asthma diagnosis. Afterwards, we detected higher level of CPA3 in BEAS-2B asthma model and asthma mice model. Besides, we proved CPA3 might activate STAT6 phosphorylation through JAK/STAT6 pathway.</p> Conclusion <p>This study has provided comprehensive insights into the molecular mechanisms underlying asthma and has identified CPA3 as a potential biomarker for the condition. In BEAS-2B cells, CPA3 has been shown to drive asthma progression by activating the JAK/STAT6 pathway, a process that can be inhibited using leflunomide.</p>

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CPA3 drives the development of asthma by promoting the activation of the JAK/STAT6 pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月23日

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  • Ke Wang,
  • Ruhao Wu,
  • Mingwei Fan,
  • Ruohan Jia,
  • Yize Liu,
  • Yue Li,
  • Pengfei Li,
  • Yu Wang,
  • Tianci Jiang,
  • Zhe Cheng

摘要

Background

Asthma is a prevalent chronic respiratory disease that affects lots of people all over the world. Characterized by multiple complex mechanisms, asthma poses substantial challenges for both patients and healthcare providers in clinical management. Comprehending the underlying mechanisms that drive the onset and progression of asthma is crucial for developing effective therapies.

Methods

The expression of CPA3 was analyzed via bioinformatics, and bulk RNA-seq datasets were utilized for this purpose. The findings were validated using quantitative real-time PCR and western blotting. A house dust mite–induced asthma mouse model was established to evaluate CPA3 expression in airway epithelial cells. Furthermore, the BEAS-2B cell line was used to investigate the potential mechanisms by which CPA3 contributes to the pathogenesis and progression of asthma.

Results

We identified four key genes from DEGs and module genes from WGCNA based on RNA-seq data of asthma. Applying random forest algorithm, we focus on CPA3 as the most significant gene in asthma diagnosis. Afterwards, we detected higher level of CPA3 in BEAS-2B asthma model and asthma mice model. Besides, we proved CPA3 might activate STAT6 phosphorylation through JAK/STAT6 pathway.

Conclusion

This study has provided comprehensive insights into the molecular mechanisms underlying asthma and has identified CPA3 as a potential biomarker for the condition. In BEAS-2B cells, CPA3 has been shown to drive asthma progression by activating the JAK/STAT6 pathway, a process that can be inhibited using leflunomide.