Neuropeptide S and its receptor aggravated asthma via TFEB dependent autophagy in bronchial epithelial cells.

IF 5.8 2区医学 Q1 Medicine

Respiratory Research Pub Date : 2025-02-10 DOI:10.1186/s12931-025-03125-9

Zhixu Wang, Peng Zhao, Gen Yan, Aijuan Sun, Li Xu, Jiao Li, Xiaorun Zhai, Xiangcen Liu, Tingting Mei, Yinghua Xuan, Yunjuan Nie

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引用次数: 0

Abstract

Background: Asthma is a prevalent respiratory disorder with limited treatment strategy. Neuropeptide S (NPS) is a highly conserved peptide via binding to its receptor NPSR, a susceptibility gene for asthma from genomics studies. However, little is known about the role of NPS-NPSR in the pathogenesis of asthma. This study was performed to determine the effect and underlying mechanism of NPS-NPSR on asthma.

Methods: NPSR knockdown was verified to affect asthma through autophagy by transcriptome sequencing and molecular biology experiments in animal models. Silencing of transcription factor EB in a bronchial epithelial cell line and validation of NPS-NPSR activation of autophagy dependent on transcription factor EB.

Results: Our results showed that NPSR expression was markedly increased in asthmatic humans and mice, mainly localized in bronchial epithelial cells. Using ovalbumin (OVA) and papain-induced asthma mouse models, NPSR-deficient mice exhibited significantly alleviated asthma, with reduced small airway lesions and inflammatory infiltration compared with wild-type mice. OVA and papain promoted TFEB-mediated autophagy with increased ATG5 and LC3 II expression, and NPS effectively regulated the activation of TFEB and autophagy. In turn, specific TFEB knockdown could restore the effect of exogenous NPS and its receptor antagonist on the autophagy and cytokines secretion in bronchial epithelial cells. Furthermore, Prkcg may be the key upstream targeting of the TFEB-autophagy pathway involved in asthma.

Conclusions: NPS-NPSR exacerbated asthma by regulating the TFEB-autophagy axis in airway epithelial injury, which may be a potential target for asthma therapy.

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来源期刊

Respiratory Research RESPIRATORY SYSTEM-

CiteScore

9.70

自引率

1.70%

发文量

314

审稿时长

4-8 weeks

期刊介绍： Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.