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Respiratory Research
Published in: Respiratory Research 1/2024

Open Access 01-12-2024 | Arterial Hypertension | Research

Neutrophil extracellular traps promote proliferation of pulmonary smooth muscle cells mediated by CCDC25 in pulmonary arterial hypertension

Authors: Hongxiao Sun, Zhanhui Du, Xu Zhang, Shuai Gao, Zhixian Ji, Gang Luo, Silin Pan

Published in: Respiratory Research | Issue 1/2024

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Abstract

Background

Previous studies have indicated that neutrophil extracellular traps (NETs) play a pivotal role in pathogenesis of pulmonary arterial hypertension (PAH). However, the specific mechanism underlying the impact of NETs on pulmonary artery smooth muscle cells (PASMCs) has not been determined. The objective of this study was to elucidate underlying mechanisms through which NETs contribute to progression of PAH.

Methods

Bioinformatics analysis was employed in this study to screen for potential molecules and mechanisms associated with occurrence and development of PAH. These findings were subsequently validated in human samples, coiled-coil domain containing 25 (CCDC25) knockdown PASMCs, as well as monocrotaline-induced PAH rat model.

Results

NETs promoted proliferation of PASMCs, thereby facilitating pathogenesis of PAH. This phenomenon was mediated by the activation of transmembrane receptor CCDC25 on PASMCs, which subsequently activated ILK/β-parvin/RAC1 pathway. Consequently, cytoskeletal remodeling and phenotypic transformation occur in PASMCs. Furthermore, the level of NETs could serve as an indicator of PAH severity and as potential therapeutic target for alleviating PAH.

Conclusion

This study elucidated the involvement of NETs in pathogenesis of PAH through their influence on the function of PASMCs, thereby highlighting their potential as promising targets for the evaluation and treatment of PAH.
Appendix
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Metadata
Title
Neutrophil extracellular traps promote proliferation of pulmonary smooth muscle cells mediated by CCDC25 in pulmonary arterial hypertension
Authors
Hongxiao Sun
Zhanhui Du
Xu Zhang
Shuai Gao
Zhixian Ji
Gang Luo
Silin Pan
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2024
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-024-02813-2

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