Stable intracellular and intercellular osmolarity is vital for all physiological processes. Although it is the first organ that receives food, the osmolarity around the mouth epithelium has never been systematically investigated. We found that oral epithelial cells are a population of ignored cells routinely exposed to hypertonic environments mainly composed of saline, glucose, etc. in vivo after chewing food. By using cultured oral epithelial cells as an in vitro model, we found that the hypotonic environments caused by both high NaCl and high glucose induced cell death in a dose- and time-dependent manner. Transcriptomics revealed similar expression profiles after high NaCl and high glucose stimulation. Most of the common differentially expressed genes were enriched in “mitophagy” and “autophagy” according to KEGG pathway enrichment analysis. Hypertonic stimulation for 1 to 6 h resulted in autophagosome formation. The activation of autophagy protected cells from high osmolarity-induced cell death. The activation of Hsp70 by the pharmacological activator handelin significantly improved the cell survival rate after hypertonic stimulation. The protective role of Hsp70 activation was partially dependent on autophagy activation, indicating a crosstalk between Hsp70 and autophagy in hypertonic stress response. The extract of the handelin-containing herb Chrysanthemum indicum significantly protected oral epithelial cells from hypertonic-induced death, providing an inexpensive way to protect against hypertonic-induced oral epithelial damage. In conclusion, the present study emphasized the importance of changes in osmolarity in oral health for the first time. The identification of novel compounds or herbal plant extracts that can activate autophagy or HSPs may contribute to oral health and the food industry.

中文翻译：

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自噬和Hsp70激活可减轻由食物引起的高渗性引起的口腔上皮细胞死亡。

稳定的细胞内和细胞间渗透压对于所有生理过程都是至关重要的。尽管它是第一个接受食物的器官，但尚未系统地研究口腔上皮周围的渗透压。我们发现，口腔上皮细胞是咀嚼食物后在体内常规暴露于高渗环境下的一组被忽略的细胞，这些高渗环境主要由盐水，葡萄糖等组成。通过使用培养的口腔上皮细胞作为体外模型，我们发现由高NaCl和高葡萄糖引起的低渗环境以剂量和时间依赖性方式诱导细胞死亡。转录组学揭示了在高NaCl和高葡萄糖刺激后相似的表达谱。根据KEGG途径富集分析，大多数常见的差异表达基因富含“有丝分裂”和“自噬”。高渗刺激1至6小时导致自噬体形成。自噬的激活保护细胞免受高渗透压诱导的细胞死亡。高渗刺激后，药理激活物handelin对Hsp70的激活显着提高了细胞存活率。Hsp70激活的保护作用部分取决于自噬激活，表明高渗应激反应中Hsp70和自噬之间的串扰。含Handelin的草药的提取物 Hsp70激活的保护作用部分取决于自噬激活，表明高渗应激反应中Hsp70和自噬之间的串扰。含Handelin的草药的提取物 Hsp70激活的保护作用部分取决于自噬激活，表明高渗应激反应中Hsp70和自噬之间的串扰。含Handelin的草药的提取物菊花可显着保护口腔上皮细胞免于高渗诱导的死亡，从而提供了一种廉价的方法来防止高渗诱导的口腔上皮损伤。总之，本研究首次强调了渗透压变化对口腔健康的重要性。可以激活自噬或HSP的新型化合物或草药提取物的鉴定可能有助于口腔健康和食品工业。