Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Catholic University of Daegu, Daegu 42472, Korea.
Department Biomedical Engineering, College of Health Science, Gachon University, Incheon 21936, Korea.
Molecules. 2022 Apr 20;27(9):2642. doi: 10.3390/molecules27092642.
Chronic rhinosinusitis (CRS) is characterized by chronic inflammation of the sinonasal mucosa with epithelial dedifferentiation toward the mesenchymal phenotype, known as the epithelial-mesenchymal transition (EMT). Asian sand dust (ASD) can induce nasal mucosal inflammation and cause the development of EMT. Korean red ginseng (KRG) and ginsenoside Rg3 have been used as traditional herbal medicines to treat various diseases. The aim of this study was to investigate their effect on ASD-induced EMT in nasal epithelial cells. Primary nasal epithelial cells were incubated with ASD with or without KRG or Rg3, and the production of transforming growth factor-β1 (TGF-β1) and interleukin (IL)-8 was measured. EMT markers were determined by RT-PCR, Western blot analysis, and confocal microscopy, and transcription factor expression by Western blot analysis. The effect on cell migration was evaluated using the wound scratch assay. Results showed ASD-induced TGF-β1 production, downregulation of E-cadherin, and upregulation of fibronectin in nasal epithelial cells. KRG and Rg3 suppressed TGF-β1 production (31.7% to 43.1%), upregulated the expression of E-cadherin (26.4% to 88.3% in mRNA), and downregulated that of fibronectin (14.2% to 46.2% in mRNA and 52.3% to 70.2% in protein). In addition, they suppressed the ASD-induced phosphorylation of ERK, p38, and mTOR, as well as inhibiting the ASD-induced migration of nasal epithelial cells (25.2% to 41.5%). The results of this study demonstrate that KRG and Rg3 inhibit ASD-induced EMT by suppressing the activation of ERK, p38, and mTOR signaling pathways in nasal epithelial cells.
慢性鼻-鼻窦炎（CRS）的特征是鼻黏膜的慢性炎症，伴有上皮向间充质表型的去分化，即上皮-间充质转化（EMT）。亚洲沙尘（ASD）可诱导鼻黏膜炎症，并导致 EMT 的发生。红参（KRG）和人参皂苷 Rg3 已被用作传统草药，用于治疗各种疾病。本研究旨在探讨其对 ASD 诱导的鼻上皮细胞 EMT 的影响。将原代鼻上皮细胞与 ASD 以及 KRG 或 Rg3 孵育，测量转化生长因子-β1（TGF-β1）和白细胞介素（IL）-8 的产生。通过 RT-PCR、Western blot 分析和共聚焦显微镜检测 EMT 标志物，Western blot 分析检测转录因子表达。通过划痕实验评估细胞迁移的影响。结果显示，ASD 诱导 TGF-β1 产生，下调鼻上皮细胞中 E-钙黏蛋白的表达，上调纤连蛋白的表达。KRG 和 Rg3 抑制 TGF-β1 的产生（31.7%至 43.1%），上调 E-钙黏蛋白的表达（mRNA 水平的 26.4%至 88.3%），下调纤连蛋白的表达（mRNA 水平的 14.2%至 46.2%和蛋白水平的 52.3%至 70.2%）。此外，它们还抑制 ASD 诱导的 ERK、p38 和 mTOR 磷酸化，以及抑制 ASD 诱导的鼻上皮细胞迁移（25.2%至 41.5%）。本研究结果表明，KRG 和 Rg3 通过抑制 ERK、p38 和 mTOR 信号通路的激活，抑制 ASD 诱导的 EMT。
