Department of Oral-facial Disorders, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan; Department of Oral and Maxillofacial Surgery 2, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Clinical Laboratory, Osaka University Dental Hospital, 1-8, Yamadaoka, Suita, Osaka, 565-0871, Japan; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, 1-7, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Biochem Biophys Res Commun. 2022 Nov 26;631:130-137. doi: 10.1016/j.bbrc.2022.09.078. Epub 2022 Sep 24.
The mammalian target of rapamycin (mTOR)-composed of multiple complexes, including mTOR complex 1/2 (mTORC1/2)-is a serine-threonine kinase that regulates embryonic development. The transcription factor, hypoxia-inducible factor-1α (HIF-1α), is also involved in embryonic development. As the relationship between mTOR and HIF-1α during embryonic development remains unclear, we investigated the relationship between the two using ex vivo submandibular salivary gland organ cultures. When the expression of HIF-1α increased under hypoxic conditions (1% O), the expression of mTOR signaling pathway-related proteins decreased. Conversely, when the expression of HIF-1α decreased, the expression of mTOR signaling pathway-related proteins increased. These results indicate a strong relationship between HIF-1α and the mTOR signaling pathway. For the first time, we clarified that HIF-1α negatively regulates the mTOR signaling pathway and suppresses salivary gland development under 1% O using small molecules. Our research provides new insights into the relationship between HIF-1α and the mTOR signaling pathway in embryonic organ development.
哺乳动物雷帕霉素靶蛋白（mTOR）由多个复合物组成，包括 mTOR 复合物 1/2（mTORC1/2）-是一种丝氨酸/苏氨酸激酶，调节胚胎发育。转录因子缺氧诱导因子-1α（HIF-1α）也参与胚胎发育。由于 mTOR 和 HIF-1α 之间在胚胎发育过程中的关系尚不清楚，我们使用离体下颌下唾液腺器官培养物研究了两者之间的关系。当 HIF-1α 在低氧条件（1% O）下表达增加时，mTOR 信号通路相关蛋白的表达减少。相反，当 HIF-1α 的表达减少时，mTOR 信号通路相关蛋白的表达增加。这些结果表明 HIF-1α 和 mTOR 信号通路之间存在很强的关系。我们首次使用小分子阐明了 HIF-1α 如何在 1% O 下负调控 mTOR 信号通路并抑制唾液腺发育。我们的研究为 HIF-1α 和 mTOR 信号通路在胚胎器官发育中的关系提供了新的见解。
