mTOR信号通路在牛乳腺上皮细胞乳脂合成中的作用与机制

乳腺上皮细胞中乳脂合成受细胞内外的信号刺激和信号转导通路的调控。mTOR信号通路是细胞生长与代谢的中心协调器，SREBP和PPAR是细胞内调控脂质合成基因表达的重要转录因子，在乳脂合成中起着关键的作用，二者的活性受到mTOR的调节，但机制并不清楚。我们前期的研究表明mTORC1调控牛乳腺上皮细胞的生长，由此假设也调控乳脂合成过程并提出了调控模型。本项目旨在探究mTOR信号通路在乳脂合成中是否发挥作用以及发挥作用的机制。拟以分子细胞生物学技术研究mTOR通路在乳脂合成中的作用，以功能基因组学技术从mRNA和蛋白两个水平上研究mTORC1对SREBP和PPARγ的调控机制及两个转录因子所调控的乳脂合成相关基因的表达。力图发现mTOR信号通路与SREBP和PPARγ之间的连接分子，最终阐明mTOR、SREBP和PPARγ、基因表达及乳脂合成之间的联系机制，为提高牛奶品质提供理论基础和技术途径。

Milk lipogenesis is stimulated by outside or intracellular signals and regulated by signaling pathway in the mammary epithelial cells. mTOR signaling pathway is a central coordinator of cell growth and metabolism. Now the facts were known that SREBP and PPARγ are important transcription factors for milk lipogenesis genes expression and their activity is regulated by mTOR, but the mechanism is not well known. Our previous work has shown that the growth of bovine mammary epithelial cells was regulated by mTORC1 and thus assumes that mTORC1 plays a key role in regulation of milk lipogenesis. The regulation model was put forward. This project aims to explore whether the mTOR signaling pathway regulates milk lipogenesis as well as the mechanism. Modern molecular and cell biology techniques will be used to explore the key role of mTOR signaling pathway in milk lipogenesis and functional genomics techniques will be used to research the mechanisms of mTORC1 acts as regulator of SREBP and PPARγ, two important transcription factors of lipogenesis related genes, both in the mRNA and proteins. We attempt to discover the intermediary molecules between mTOR signaling pathway and SREBP or PPARγ. Eventually, we hope to clarify the connective mechanism between mTOR, SREBP and PPARγ, genes expression and milk lipogenesis. These data will provide a theoretical basis and technological approaches for improving the quality of milk.