Role of the mTOR signalling pathway in salivary gland development
Role of the mTOR signalling pathway in salivary gland development
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DOI：
10.1111/febs.14937
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发表时间：
2019-09-01
期刊：
影响因子：
5.4
通讯作者：
Sakai, Takayoshi
中科院分区：
文献类型：
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作者：
Sakai, Manabu;Fukumoto, Moe;Sakai, Takayoshi
唾液腺发育的特点是广泛的分支形态发生。尽管多种分子与唾液腺发育有关，但哺乳动物雷帕霉素靶蛋白 (mTOR) 信号通路（包括 mTOR 复合物 1 和 2（mTORC1 和 2））在唾液腺发育中的作用尚不清楚。在这里，我们使用离体下颌下唾液腺 (SMG) 器官培养物检查了与 mTOR 信号通路相关的蛋白质表达水平。我们发现，雷帕霉素（一种 mTOR 抑制剂）可显着减少唾液腺中的分枝芽，并抑制 mTORC1 信号通路相关蛋白（mTOR、p70 核糖体蛋白 S6 激酶 1 和真核起始因子 4E 结合蛋白 1）的磷酸化。此外，AKT 是 mTORC1 的上游蛋白激酶，也是 mTORC2 的下游，可被 LY294002（一种磷脂酰肌醇 3-激酶抑制剂）抑制，但不会被雷帕霉素抑制。此外，与媒介物处理的新生小鼠相比，雷帕霉素处理的ICR新生小鼠的体重和唾液腺均有所减少。目前的数据表明，mTOR 信号通路（包括 mTORC1 和 mTORC2）在离体 SMG 器官培养和体内 ICR 新生小鼠唾液腺发育中发挥着关键作用。
Development of the salivary gland is characterized by extensive branching morphogenesis. Although various molecules have been implicated in salivary gland development, the role of the mammalian target of rapamycin (mTOR) signalling pathway, including both mTOR complexes 1 and 2 (mTORC1 and 2), in salivary gland development is unknown. Here, we examined protein expression levels related to the mTOR signalling pathway using an ex vivo submandibular salivary gland (SMG) organ culture. We showed that branching buds in the salivary glands were substantially decreased and phosphorylation of mTORC1 signalling pathway related proteins (mTOR, p70 ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1) was inhibited by rapamycin (an mTOR inhibitor). In addition, AKT, which is an upstream protein kinase of mTORC1 and is downstream of mTORC2, is inhibited by LY294002 (a phosphatidylinositol 3-kinase inhibitor), but not by rapamycin. Moreover, rapamycin-treated ICR neonatal mice exhibited a reduction in both body weight and salivary glands compared with vehicle-treated neonatal mice. The present data indicate that the mTOR signalling pathway, including both mTORC1 and mTORC2, plays a critical role in salivary gland development both in ex vivo SMG organ culture and ICR neonatal mice in vivo.