School of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Toxicol Appl Pharmacol. 2021 May 15;419:115517. doi: 10.1016/j.taap.2021.115517. Epub 2021 Apr 1.
Cleft palate (CP) is a common birth defect with a high incidence of occurrence in humans. The 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic halogenated aromatic hydrocarbon, with a strong CP effect on mice. Increasing recent evidences have shown that long-noncoding RNAs (lncRNAs) play an important role in several diseases, including CP. However, there is a paucity of studies on the role of lncRNA MEG3 in the occurrence and development of TCDD-induced CP. In this study, the relationship between MEG3 and the proliferation of palatal mesenchymal cells and the underlying molecular mechanism were studied by establishing fetal CP with TCDD (64 μg/kg) in C57BL/6N mice. The results revealed that MEG3 was highly expressed during the critical period of CP formation and that the fetal mesenchymal proliferation was significantly inhibited at certain critical periods in the mice receiving TCDD. In addition, we noted a possibility of a crosstalk between MEG3 and the TGF-β/Smad pathway, such that the inhibition of the TGF-β/Smad pathway was induced by TCDD. Cumulatively, our study suggests that TCDD-induced CP may be caused by MEG3 inhibition of the proliferation of palatal mesenchymal cells involving the TGFβ/Smad pathway, which may provide a novel perspective to understand the pathogenesis of CP.
腭裂（CP）是一种常见的出生缺陷，在人类中发病率很高。2,3,7,8-四氯二苯并对二恶英（TCDD）是一种高毒性卤代芳烃，对小鼠具有强烈的 CP 作用。越来越多的证据表明，长非编码 RNA（lncRNA）在包括 CP 在内的多种疾病中发挥重要作用。然而，lncRNA MEG3 在 TCDD 诱导的 CP 发生和发展中的作用研究甚少。在这项研究中，通过用 TCDD（64μg/kg）在 C57BL/6N 小鼠中建立胎儿 CP，研究了 MEG3 与腭间充质细胞增殖的关系及其潜在的分子机制。结果表明，MEG3 在 CP 形成的关键时期表达量较高，而 TCDD 处理的小鼠在某些关键时期，胎儿间充质增殖受到明显抑制。此外，我们注意到 MEG3 与 TGF-β/Smad 通路之间可能存在相互作用，即 TCDD 诱导 TGF-β/Smad 通路的抑制。综上所述，我们的研究表明，TCDD 诱导的 CP 可能是由 MEG3 抑制涉及 TGFβ/Smad 通路的腭间充质细胞增殖引起的，这可能为理解 CP 的发病机制提供新的视角。
