1. S100A11 regulates nasal epithelial cell remodeling and inflammation in CRSwNPs via the RAGE-mediated AMPK-STAT3 pathway.
- Author
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Liu, Chengcheng, Du, Hongjie, Wang, Yajie, Gong, Ningyue, Qi, Wenwen, Zhou, Xiangmin, and Shi, Li
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EPITHELIAL cells , *RHINITIS , *CELLULAR signal transduction , *SMALL interfering RNA , *EPITHELIUM , *NASAL mucosa - Abstract
• S100A11 is highly expressed in chronic rhinitis and sinusitis with nasal polyps (CRSwNPs). • Upregulation of S100A11 expression inhibits proliferation and promotes apoptosis and inflammation of nasal epithelial cells. • S100A11 can activate the AMPK signaling pathway and inhibit the STAT3 signaling pathway in a RAGE-mediated manner. • S100A11 plays an important role in nasal mucosal epithelial remodeling and inflammation of CRSwNPs. Abnormal remodeling of the nasal mucosal epithelium and persistent chronic inflammation are important pathological features of chronic sinusitis with nasal polyps (CRSwNPs). In order to explore the molecular regulation mechanism of CRSwNPs, we performed iTRAQ protein profile analysis on 18 clinical samples collected (9 patients with nasal polyps and 9 healthy patients) and found that S100A11, a Ca2+-binding protein, was significantly higher in CRSwNPs. Subsequently, we demonstrated that S100A11 was mainly located in nasal mucosal epithelial cells and is up-regulated in human nasal epithelial stem/progenitor cells (hNESPCs) from CRSwNPs patients and CRSwNPs epithelial cell model established with S. aureus. To determine the functional role of S100A11 and the signal pathways in epithelial cells, we constructed S100A11 overexpression vector, small interfering RNA, recombinant protein-S100A11 (rh-S100A11) and RAGE inhibitor (sRAGE). Results showed that upregulation of S100A11 inhibited epithelial cell viability and promoted apoptosis and inflammation, in addition, S100A11 can regulate the signal homeostasis of AMPK-STAT3 via RAGE mediation in epithelial cells. Our findings suggest that S100A11 is involved in CRSwNPs epithelial tissue remodeling and inflammatory response regulation and may be a useful target for CRSwNPs therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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