Negative feedback by SNAI2 regulates TGFβ1‐induced amelotin gene transcription in epithelial–mesenchymal transition
Negative feedback by SNAI2 regulates TGFβ1‐induced amelotin gene transcription in epithelial–mesenchymal transition
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DOI：
10.1002/jcp.27804
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发表时间：
2018-11
影响因子：
5.6
通讯作者：
Y. Nakayama;Yuto Tsuruya;Keisuke Noda;Mizuho Yamazaki-Takai;Yasunobu Iwai;B. Ganss;Y. Ogata
中科院分区：
文献类型：
--
作者：
Y. Nakayama;Yuto Tsuruya;Keisuke Noda;Mizuho Yamazaki-Takai;Yasunobu Iwai;B. Ganss;Y. Ogata
结合上皮（JE）表现出生物学反应与牙龈上皮细胞的快速更新。这种状态发生在牙龈炎症和牙周治疗后的伤口愈合。为了了解乙脑的潜在机制并维持乙脑的稳态，研究乙脑特异性基因的作用是很重要的。Amelotin（AMTN）定位于JE并受炎性细胞因子和凋亡因子的调节，其在稳定口腔细菌的入口--牙-龈附着中发挥关键作用。在这项研究中，我们证明了AMTN基因表达受SNAI 2和转化生长因子β1（TGFβ1）诱导的上皮-间质转化（EMT）的调节，EMT发生在慢性炎症期间的伤口愈合和纤维化中。在牙龈上皮细胞的EMT中，SNAI 2通过与小鼠AMTN基因启动子中的E盒（E2和E4）结合来下调AMTN基因表达。同时，TGFβ1诱导的AMTN基因表达被SNAI 2和TGFβ1诱导的SNAI 2减弱，而不抑制TGFβ1-Smad 3信号通路。此外，SNAI 2小干扰RNA（siRNA）挽救了SNAI 2诱导的AMTN基因表达下调，SNAI 2 siRNA增强了TGFβ1诱导的AMTN基因表达。综上所述，这些数据表明，AMTN基因的表达在EMT的促进被SNAI 2下调。AMTN基因表达的抑制作用是对TGFβ1-Smad 3信号通路的独立反馈，表明该机制可能参与维持JE和伤口愈合期牙龈上皮细胞的稳态。
Junctional epithelium (JE) demonstrates biological responses with the rapid turnover of gingival epithelial cells. The state occurs in inflammation of gingiva and wound healing after periodontal therapy. To understand the underlying mechanisms and to maintain homeostasis of JE, it is important to investigate roles of JE‐specific genes. Amelotin (AMTN) is localized at JE and regulated by inflammatory cytokines and apoptotic factors that represent a critical role of AMTN in stabilizing the dentogingival attachment, which is an entrance of oral bacteria. In this study, we demonstrated that the AMTN gene expression was regulated by SNAI2 and transforming growth factor β1 (TGFβ1)‐induced epithelial–mesenchymal transition (EMT) that occurs in wound healing and fibrosis during chronic inflammation. SNAI2 downregulated AMTN gene expression via SNAI2 bindings to E‐boxes (E2 and E4) in the mouse AMTN gene promoter in EMT of gingival epithelial cells. Meanwhile, TGFβ1‐induced AMTN gene expression was attenuated by SNAI2 and TGFβ1‐induced SNAI2, without inhibition of the TGFβ1‐Smad3 signaling pathway. Moreover, SNAI2 small interfering RNA (siRNA) rescued SNAI2‐induced downregulation of AMTN gene expression, and TGFβ1‐induced AMTN gene expression was potentiated by SNAI2 siRNA. Taken together, these data demonstrated that AMTN gene expression in the promotion of EMT was downregulated by SNAI2. The inhibitory effect of AMTN gene expression was an independent feedback on the TGFβ1‐Smad3 signaling pathway, suggesting that the mechanism can be engaged in maintaining homeostasis of gingival epithelial cells at JE and the wound healing phase.