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

Abstract

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% O₂), 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% O₂ using small molecules. Our research provides new insights into the relationship between HIF-1α and the mTOR signaling pathway in embryonic organ development.

Keywords: Development; HIF-1α; Hypoxia; Salivary glands; mTOR signaling.