The role of MEG3 in the proliferation of palatal mesenchymal cells is related to the TGFβ/Smad pathway in TCDD inducing cleft palate

• Published in: Toxicology and applied pharmacology 2021-05, Vol.419, p.115517, Article 115517
• Main Authors: He, Zhidong, Liu, XinXin, Liu, Xiaozhuan, Cui, Lingling, Yuan, Yangyang, Zhang, Huanhuan, Chen, Yao, Tao, Yuchang, Yu, Zengli
• Format: Article
• Language: English
• Subjects: 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD); Animals; Cell Proliferation; Cleft palate; Cleft Palate - chemically induced; Cleft Palate - genetics; Cleft Palate - metabolism; Cleft Palate - pathology; Disease Models, Animal; Female; Gene Expression Regulation, Developmental; Gestational Age; MEG3; Mesenchymal Stem Cells - metabolism; Mesenchymal Stem Cells - pathology; Mice; Mice, Inbred C57BL; Palate, Hard - abnormalities; Palate, Hard - metabolism; Phosphorylation; Polychlorinated Dibenzodioxins; Pregnancy; Proliferation; Receptor, Transforming Growth Factor-beta Type I - genetics; Receptor, Transforming Growth Factor-beta Type I - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Smad Proteins - metabolism; TGF-β/Smad; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2021.115517

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. •TCDD exposure inhibited the fetal mesenchymal proliferation in mice and may induce the occurrence of cleft palate.•TCDD exposure promoted the expression of MEG3 and induce cleft palate probably not by altering the MEG3 methylation levels.•MEG3 may represses palatal mesenchymal cell proliferation via the TGFβ/Smad pathway.