Evidence map›Paper›PMID 40001511›Full record

ArticleBiomolecules2025

PAR2 Participates in the Development of Cough Hypersensitivity in Guinea Pigs by Regulating TRPA1 Through PKC.

Yiqing Zhu, Tongyangzi Zhang, Haodong Bai, Wanzhen Li, Shengyuan Wang, Xianghuai Xu, Li Yu

Abstract read
In one paragraph

Article in Biomolecules, 2025. 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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5 · Who and what money

Authors and funding

7 authors.

Yiqing ZhuDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
Tongyangzi ZhangDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.ORCID 0000-0002-4375-0499
Haodong BaiDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
Wanzhen LiDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
Shengyuan WangDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.ORCID 0000-0003-1245-2998
Xianghuai XuDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.ORCID 0000-0002-8713-5332
Li YuDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.

Funding

National Natural Science Foundation of China No. 82270114 and 82070102Program of Shanghai Academic Research Leader No. 22XD1422700Science and Technology Commission of Shanghai Municipality No.22Y11901300Shanghai Municipal Health Commission Clinical Research No. 20244Y0147
6 · The paper itself

Abstract

objectiveThis study was conducted to validate the involvement of the PAR2-PKC-TRPA1 pathway in cough hypersensitivity (CHS) development.

methodsGuinea pigs were divided into a blank control, a citric acid-induced enhanced cough model, and drug intervention groups. The effects of the drugs on capsaicin-induced cough responsiveness in a cough model were observed. The effects of individual and combined treatments (including PAR2 agonists, TRPA1 agonists, PAR2 antagonists, TRPA1 antagonists, PKC agonists, and PKC antagonists) on PAR2, phospho-PKC (pPKC), and TRPA1 expression in bronchial tissues and the vagus ganglion (jugular and nodose) in the cough model and control groups were assessed. Additionally, whole-cell patch-clamp recordings were conducted to evaluate the effects of the drugs on vagus ganglion neuron electrophysiological activity.

results① Both PAR2 antagonists and TRPA1 antagonists significantly reduced cough frequency in guinea pigs with a cough, and the PAR2 antagonist inhibited coughing induced by the TRPA1 agonist. ② Western blotting and multiplex immunohistochemistry (mIHC) indicated that PAR2, pPKCα, PKCα, and TRPA1 expression in bronchial and vagus ganglion tissues was elevated in the cough model compared with the control, with TRPA1 expression being regulated by PAR2 and PKC being involved in this regulatory process. ③ Whole-cell patch-clamp recordings demonstrated that TRPA1 agonists induced an inward current in nodose ganglion neurons, which was further amplified by PAR2 agonists; this amplification effect was blocked by PKC antagonist. Additionally, PAR2 antagonists inhibited the inward current induced by TRPA1 agonists. ④ At various concentrations, including the optimal antitussive concentration, PAR2 antagonists did not significantly affect pulse amplitude, arterial oxygen saturation, heart rate, body temperature, or respiratory rate in guinea pigs.

conclusionPAR2 regulates TRPA1 through PKC in cough syndrome (CHS) pathogenesis, making targeting PAR2 a safe and effective therapeutic strategy for CHS.

Indexed as

CoughHypersensitivityProtein Kinase CReceptor, PAR-2TRPA1 Cation ChannelAnimalsCapsaicinDisease Models, AnimalGuinea PigsMaleNodose GanglionCapsaicinProtein Kinase CReceptor, PAR-2TRPA1 Cation Channelchronic coughcough hypersensitivityPAR2TRPA1whole-cell patch-clamp

Identifiers

PMID40001511
PMCPMC11853178

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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.