| First Author | Cheng J | Year | 2019 |
| Journal | Inflammation | Volume | 42 |
| Issue | 4 | Pages | 1370-1382 |
| PubMed ID | 31028575 | Mgi Jnum | J:295762 |
| Mgi Id | MGI:6454359 | Doi | 10.1007/s10753-019-00998-z |
| Citation | Cheng J, et al. (2019) Desmoglein 3 Silencing Inhibits Inflammation and Goblet Cell Mucin Secretion in a Mouse Model of Chronic Rhinosinusitis via Disruption of the Wnt/beta-Catenin Signaling Pathway. Inflammation 42(4):1370-1382 |
| abstractText | 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-alpha, IL-6, and IL-8 were measured by ELISA. In addition, loss-of-function experiment was conducted using siRNAs targeting DSG3 and beta-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/beta-catenin signaling pathway was analyzed by determining the mRNA and protein levels of DSG3, Wnt, beta-catenin, and GSK3beta. 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 beta-catenin silencing could decrease the levels of TNF-alpha, IL-6, and IL-8, and the positive rates of MUC5B and MUC5AC while enhancing goblet cell apoptosis. The Wnt/beta-catenin signaling pathway was blocked by DSG3, evidenced by downregulated Wnt and beta-catenin as well as upregulated GSK3beta mRNA and protein levels. Overall, this study provides evidence that silencing DSG3 could inhibit the activation of the Wnt/beta-catenin signaling pathway, thus alleviating CRS. |
