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Evidence for role of acid-sensing ion channel 1a in chronic rhinosinusitis with nasal polyps

  • Rhinology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Purpose

A variety of inflammatory cells are infiltrated histologically in sinonasal mucosa of chronic rhinosinusitis with nasal polyps (CRSwNP), especially CRSwNP with asthma. Acid-sensing ion channel 1a (ASIC1a) is essential in the process of sensing acidification and triggering inflammation. Whereas, its role and mechanism in CRSwNP remain uncertain. The present study aimed to explore the roles and mechanism of ASIC1a in the pathogenesis of CRSwNP.

Methods

Nasal secretions from control subjects, patients with CRSwNP with or without asthma were collected for measuring pH values. Western blotting, real-time PCR and immunohistochemistry (IHC) were employed to assess ASIC1a expression in nasal tissue samples from included subjects. The co-localization of ASIC1a with inflammatory cells was evaluated by immunofluorescence staining. Then, dispersed nasal polyp cells (DNPCs) were cultured under acidified condition (pH 6.0), with or without ASIC1a inhibitor amiloride. Western blotting, real-time PCR, LDH activity kit, and ELISA were performed to assess the effects and mechanisms of stimulators on the cells.

Results

The pH values were significantly lower in the nasal secretions from patients with CRSwNP with asthma. Significant upregulation of ASIC1a protein, mRNA levels, and positive cells was found in CRSwNP with asthma. ASIC1a was detected in a variety of inflammatory cells. In cultured DNPCs, significant alterations of ASIC1a levels, LDH activity, HIF-1α levels, and inflammatory cytokines were found under acidified condition (pH 6.0), but were prevented by amiloride.

Conclusion

Upregulation of ASIC1a might be essential in the process of sensing acidification and triggering inflammatory response via enhancing HIF-1α expression and LDH activity to activate inflammatory cells in the pathogenesis of CRSwNP, especially in CRSwNP with asthma.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81870700, 82071014 and 82000951), Shanghai Natural Science Foundation of China (No. 16ZR1426100), Science and Technology Innovation Action Plan of Science and Technology Commission of Shanghai Municipality (No. 19411950700) and the Key Laboratory Funding of Science and Technology Commission of Shanghai Municipality (No. 18DZ2260200).

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Author notes

  1. Ru Tang and Guangyi Ba contributed equally to this work.

Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, No. 600 Yishan Road, Shanghai, 200233, People’s Republic of China

    Ru Tang, Guangyi Ba, Mingxian Li, Zhipeng Li, Haibo Ye, Hai Lin & Weitian Zhang

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  1. Ru Tang
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  2. Guangyi Ba
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Correspondence to Hai Lin or Weitian Zhang.

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The authors have no other funding, fnancial relationships or conflicts of interest to disclose.

Ethical approval

All procedures performed in the study were approved by the Ethical Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital (No. 2019-KY-039(K)).

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Informed consent was obtained from all individual participants included in the study.

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Tang, R., Ba, G., Li, M. et al. Evidence for role of acid-sensing ion channel 1a in chronic rhinosinusitis with nasal polyps. Eur Arch Otorhinolaryngol 278, 2379–2386 (2021). https://doi.org/10.1007/s00405-020-06521-7

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