Department of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Department of Otolaryngology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Front Immunol. 2022 Jan 28;13:835888. doi: 10.3389/fimmu.2022.835888. eCollection 2022.
Epithelial-mesenchymal transition (EMT) is thought to be involved in the tissue remodeling and long-term inflammatory process of chronic sinusitis (CRS), but the driving mechanism is still unclear. Using high-resolution mass spectrometry, we performed a proteomic screen of CRS nasal mucosal tissue to identify differentially expressed proteins. Data are available ProteomeXchange with identifier PXD030884. Specifically, we identified S100 calcium binding protein A4 (S100A4), an effective factor in inflammation-related diseases, and its downstream protein closely related to tissue fibrosis collagen type I alpha 1 chain (COL1A1), which suggested its involvement in nasal mucosal tissue remodeling. In addition, stimulation of human nasal epithelial cells (HNEpCs) with lipopolysaccharide (LPS) mimicked the inflammatory environment of CRS and showed that S100A4 is involved in regulating EMT and thus accelerating tissue remodeling in the nasal mucosa, both in terms of increased cell motility and overexpression of mesenchymal-type proteins. Additionally, we further investigated the regulation mechanism of S100A4 involved in EMT in CRS. Our research results show that in the inflammatory environment of CRS nasal mucosal epithelial cells, TCF-4 will target to bind to S100A4 and regulate its transcription. The transcription of S100A4 in turn affects the execution of the important signaling pathway in EMT, the Wnt/GSK-3β/β-catenin pathway, through the TCF-4/β-catenin complex. In conclusion, this study confirmed that the expression of S100A4 was significantly increased during the progressive EMT process of CRS mucosal epithelial cells, and revealed that the transcriptional regulation of S100A4 plays an important role in the occurrence and development of EMT. This finding will help us to better understand the pathogenesis behind the remodeling in CRS patients, and identify target molecules for the treatment of CRS.
上皮-间充质转化（EMT）被认为参与慢性鼻窦炎（CRS）的组织重塑和长期炎症过程，但驱动机制尚不清楚。我们使用高分辨率质谱法对 CRS 鼻黏膜组织进行蛋白质组筛选，以鉴定差异表达蛋白。数据可在 ProteomeXchange 中以标识符 PXD030884 获得。具体来说，我们鉴定了 S100 钙结合蛋白 A4（S100A4），它是炎症相关疾病的有效因子，以及与其下游与组织纤维化密切相关的胶原蛋白 I 型α 1 链（COL1A1），这表明它参与了鼻黏膜组织重塑。此外，用脂多糖（LPS）刺激人鼻上皮细胞（HNEpCs）模拟了 CRS 的炎症环境，表明 S100A4 参与调节 EMT，从而加速鼻黏膜组织重塑，这表现在细胞迁移能力增强和间充质型蛋白过表达。此外，我们进一步研究了 S100A4 参与 CRS 中 EMT 的调节机制。我们的研究结果表明，在 CRS 鼻黏膜上皮细胞的炎症环境中，TCF-4 将靶向结合 S100A4 并调节其转录。S100A4 的转录反过来又通过 TCF-4/β-catenin 复合物影响 EMT 中重要信号通路 Wnt/GSK-3β/β-catenin 途径的执行。总之，本研究证实 S100A4 的表达在 CRS 黏膜上皮细胞进行性 EMT 过程中显著增加，并揭示了 S100A4 的转录调节在 EMT 的发生和发展中起重要作用。这一发现将有助于我们更好地了解 CRS 患者重塑的发病机制，并确定 CRS 治疗的靶分子。
