Department of Burn and Plastic Surgery Children's hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Pediatrics.
Toxicol Lett. 2020 Oct 15;333:90-96. doi: 10.1016/j.toxlet.2020.08.001. Epub 2020 Aug 5.
2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) effectively induces cleft palate at increased doses, but its mechanism of involvement is unclear, and arguments have examined palatal shelf contact and/or fusion failure. The role of different types of cells constituting palatal skulls remains elusive regarding TCDD dosage. No reports have simultaneously compared the biological behaviors of TCDD- induced mesenchymal and epithelial cells in vitro. This study employed primary epithelial and mesenchymal cells as models in vitro to explore proliferation, migration, apoptosis and epithelial-to-mesenchymal transition with two different doses of TCDD (10 nmol/L, 100 nmol/L), contrasted with a control group without TCDD. Interestingly, we found the EMT process of primary palatal epithelial cells occurred automatically in vitro without helping bilateral palatal contact. The results showed that, with the low dose of TCDD, transformation of epithelial cells to mesenchymal cells was inhibited, and mesenchymal cell proliferation and migration were promoted. At high doses, mesenchymal cells decreased, preventing palate development, uprising and contact, while the EMT of epithelial cells decreased. Regardless of dose of TCDD, no impact on migration and apoptosis of epithelial cells was noted, but there was increased apoptosis of mesenchymal cell in a dose-dependent manner.
2,3,7,8-四氯二苯并对二恶英(TCDD)在高剂量下有效地诱导腭裂,但它的参与机制尚不清楚,有观点认为涉及腭突的接触和/或融合失败。关于 TCDD 剂量,构成腭颅的不同类型细胞的作用仍不清楚。目前尚无报道同时比较 TCDD 诱导的间质和上皮细胞在体外的生物学行为。本研究采用原代上皮和间充质细胞作为体外模型,探讨了两种不同剂量的 TCDD(10 nmol/L,100 nmol/L)对增殖、迁移、凋亡和上皮-间充质转化的影响,并与未加 TCDD 的对照组进行了比较。有趣的是,我们发现原代腭上皮细胞的 EMT 过程在体外自动发生,无需帮助双侧腭突接触。结果表明,低剂量 TCDD 抑制上皮细胞向间充质细胞的转化,促进间充质细胞的增殖和迁移。高剂量时,间充质细胞减少,阻止腭的发育、隆起和接触,同时上皮细胞的 EMT 减少。无论 TCDD 剂量如何,对上皮细胞的迁移和凋亡均无影响,但间充质细胞的凋亡呈剂量依赖性增加。