HIF-1a regulates mTOR signaling pathway during salivary gland development

The mammalian target of rapamycin (mTOR)dcomposed of multiple complexes, including mTOR complex 1/2 (mTORC1/2)dis a serine-threonine kinase that regulates embryonic development. The transcription factor, hypoxia-inducible factor-1a (HIF-1a), is also involved in embryonic development. As the relationship between mTOR and HIF-1a 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-1a increased under hypoxic conditions (1% O2), the expression of mTOR signaling pathway-related proteins decreased. Conversely, when the expression of HIF-1a decreased, the expression of mTOR signaling pathway-related proteins increased. These results indicate a strong rela-tionship between HIF-1a and the mTOR signaling pathway. For the first time, we clarified that HIF-1a negatively regulates the mTOR signaling pathway and suppresses salivary gland development under 1% O2 using small molecules. Our research provides new insights into the relationship between HIF-1a and the mTOR signaling pathway in embryonic organ development.(c) 2022 Elsevier Inc. All rights reserved.