S100A4/TCF Complex Transcription Regulation Drives Epithelial-Mesenchymal Transition in Chronic Sinusitis Through...

Area of Science:

• Immunology and Inflammation
• Cell Biology and Signaling
• Otorhinolaryngology

Background:

• Epithelial-mesenchymal transition (EMT) is implicated in chronic sinusitis (CRS) tissue remodeling and inflammation.
• The precise molecular mechanisms driving EMT in CRS remain incompletely understood.

Purpose of the Study:

• To identify key proteins involved in CRS pathogenesis using proteomic analysis.
• To elucidate the role and regulatory mechanisms of S100A4 in EMT within CRS nasal mucosa.

Main Methods:

• High-resolution mass spectrometry for proteomic screening of CRS nasal mucosal tissue.
• Stimulation of human nasal epithelial cells (HNEpCs) with lipopolysaccharide (LPS) to mimic CRS inflammation.
• Investigation of S100A4 transcriptional regulation by TCF-4 and its impact on the Wnt/GSK-3β/β-catenin pathway.

Main Results:

• S100 calcium binding protein A4 (S100A4) and collagen type I alpha 1 chain (COL1A1) were identified as differentially expressed proteins.
• S100A4 stimulation in HNEpCs promoted EMT, increasing cell motility and mesenchymal markers.
• TCF-4 was found to regulate S100A4 transcription, which in turn influences the Wnt/GSK-3β/β-catenin pathway via a TCF-4/β-catenin complex.

Conclusions:

• S100A4 expression is significantly increased during EMT in CRS mucosal epithelial cells.
• Transcriptional regulation of S100A4 is crucial for the development and progression of EMT in CRS.
• S100A4 represents a potential therapeutic target for mitigating CRS-associated tissue remodeling.