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Desmoglein 3 Silencing Inhibits Inflammation and Goblet Cell Mucin Secretion in a Mouse Model of Chronic Rhinosinusitis via Disruption of the Wnt/β-Catenin Signaling Pathway

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Abstract

Chronic rhinosinusitis (CRS) is a common disease characterized by inflammation of the nose and paranasal sinuses lasting over 12 weeks. This study aims to evaluate the effect of desmoglein 3 (DSG3) on inflammatory response and goblet cell mucin secretion in a mouse model of CRS. The CRS-related differentially expressed genes and disease genes were screened using microarray-based gene expression analysis. Subsequently, CRS mouse models were established. The levels of pro-inflammatory factors TNF-α, IL-6, and IL-8 were measured by ELISA. In addition, loss-of-function experiment was conducted using siRNAs targeting DSG3 and β-catenin. The secretion of mucins MUC5B and MUC5AC in goblet cells was detected, and the apoptosis of goblet cells was assessed. The regulatory effect of DSG3 on the Wnt/β-catenin signaling pathway was analyzed by determining the mRNA and protein levels of DSG3, Wnt, β-catenin, and GSK3β. DSG3 was identified to be an upregulated gene in CRS, which was further documented in CRS mice models. Elevated inflammation and mucin production were noted in CRS mice models. Also, it was found that DSG3 or β-catenin silencing could decrease the levels of TNF-α, IL-6, and IL-8, and the positive rates of MUC5B and MUC5AC while enhancing goblet cell apoptosis. The Wnt/β-catenin signaling pathway was blocked by DSG3, evidenced by downregulated Wnt and β-catenin as well as upregulated GSK3β mRNA and protein levels. Overall, this study provides evidence that silencing DSG3 could inhibit the activation of the Wnt/β-catenin signaling pathway, thus alleviating CRS.

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Acknowledgements

We acknowledge and appreciate our colleagues for their valuable efforts and comments on this paper.

Funding

This work is supported by Medical and Health Project of Jilin Science and Technology Development Plan (No. 20190304037YY).

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Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun, 130000, Jilin Province, People’s Republic of China

    Jinzhang Cheng, Jingpu Yang, Kai Xue, Yin Zhao, Chang Zhao, Song Li & Zonggui Wang

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  1. Jinzhang Cheng
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Correspondence to Zonggui Wang.

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Cheng, J., Yang, J., Xue, K. et al. Desmoglein 3 Silencing Inhibits Inflammation and Goblet Cell Mucin Secretion in a Mouse Model of Chronic Rhinosinusitis via Disruption of the Wnt/β-Catenin Signaling Pathway. Inflammation 42, 1370–1382 (2019). https://doi.org/10.1007/s10753-019-00998-z

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