microRNA-875-5p plays critical role for mesenchymal condensation in epithelial-mesenchymal interaction during tooth development
microRNA-875-5p plays critical role for mesenchymal condensation in epithelial-mesenchymal interaction during tooth development
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DOI：
10.1038/s41598-020-61693-w
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发表时间：
2020-03-18
影响因子：
4.6
通讯作者：
Fukumoto, Satoshi
中科院分区：
文献类型：
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作者：
Funada, Keita;Yoshizaki, Keigo;Fukumoto, Satoshi
上皮-间充质相互作用对包括牙齿在内的器官发育具有关键作用，在此期间，上皮增厚和间充质凝结通过信号通路的精确调节而启动。在牙齿中，表达PDGF受体的神经嵴来源的间充质细胞迁移并向内陷上皮聚集。为了确定这种相互作用的分子机制，我们使用基因表达帽分析（CAGE）来探索牙齿器官的特异性转录起始位点（TSS）。我们在染色体15 qD 1区域检测到牙齿特异性TSS，其编码microRNA-875（mir 875）。MiR 875 - 5 p在牙齿发育早期的牙间充质中特异性表达。此外，PRRX 1/2与mir 875启动子区结合并增强mir 875的表达。为了评估miR 875 - 5 p在牙齿间充质中的作用，我们将模拟miR 875 - 5 p转染到小鼠牙髓（mDP）细胞中，这表明miR 875 - 5 p通过PDGF信号通路显著诱导细胞向牙齿上皮细胞迁移。这些结果还表明，miR 875 - 5 p通过抑制PTEN和STAT 1诱导细胞迁移，而PTEN和STAT 1作为转录后调节的一部分由miR 875 - 5 p调节。总之，我们的研究结果表明，牙齿特异性miR 875 - 5 p在内陷牙上皮周围的间充质细胞的细胞凝聚和上皮-间充质相互作用的诱导中具有重要作用。
Epithelial-mesenchymal interaction has critical roles for organ development including teeth, during which epithelial thickening and mesenchymal condensation are initiated by precise regulation of the signaling pathway. In teeth, neural crest-derived mesenchymal cells expressed PDGF receptors migrate and become condensed toward invaginated epithelium. To identify the molecular mechanism of this interaction, we explored the specific transcriptional start sites (TSSs) of tooth organs using cap analysis of gene expression (CAGE). We identified a tooth specific TSS detected in the chromosome 15qD1 region, which codes microRNA-875 (mir875). MiR875-5p is specifically expressed in dental mesenchyme during the early stage of tooth development. Furthermore, PRRX1/2 binds to the mir875 promoter region and enhances the expression of mir875. To assess the role of miR875-5p in dental mesenchyme, we transfected mimic miR875-5p into mouse dental pulp (mDP) cells, which showed that cell migration toward dental epithelial cells was significantly induced by miR875-5p via the PDGF signaling pathway. Those results also demonstrated that miR875-5p induces cell migration by inhibiting PTEN and STAT1, which are regulated by miR875-5p as part of post-transcriptional regulation. Together, our findings indicate that tooth specific miR875-5p has important roles in cell condensation of mesenchymal cells around invaginated dental epithelium and induction of epithelial-mesenchymal interaction.