低氧诱导的滋养细胞自噬对DCs生物物理特性及其功能的影响与机制

项目名称： 低氧诱导的滋养细胞自噬对DCs生物物理特性及其功能的影响与机制

项目编号： No.31270971

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 曲迅

作者单位： 山东大学

项目金额： 80万元

中文摘要： 妊娠是机体一个复杂的生理过程。尤其是孕早期，在胚泡植入及胎盘形成过程中涉及了诸多受精细调控的生物学现象，从而维持妊娠的成功。低氧张力是妊娠早期特征性微环境之一，滋养细胞是低氧感受的直接"应答"细胞，也是调控其他免疫细胞如DCs的重要"驯化"细胞。但低氧如何调控滋养细胞进而影响DCs分化与功能目前尚不清楚。文献已证实细胞在氧耗竭等应激条件下可诱导自噬，并可通过自噬参与调控机体的许多生理及病理生理过程。本项目拟利用GFP-LC3重组质粒稳定转染的人滋养细胞系HTR-8/SVneo细胞，研究低氧对其自噬的影响及机制，并进一步探讨滋养层细胞自噬改变后，对DCs细胞生物物理特性的影响及调控DCs分化及功能的机制。研究结果将进一步丰富妊娠植入过程的机制；并可拓宽免疫学研究领域的视角，从细胞生物物理特性方面解析DCs的分化及其功能的调控与机制，将为基于DCs的疫苗制备及应用提供新的靶点。

中文关键词： 滋养层细胞；低氧；自噬；树突状细胞；髓系来源抑制细胞

英文摘要： Pregnancy is a complicated and fine physiological process. The appropriate modulation of numerous biological phenomena involved in implantation and placentation during the early pregnancy is pivotal to a successful pregnancy . Hypoxia is one of the most unique characteristics in the early pregnancy microenvironment, and trophoblastic cells, which give rise to responses directly to hypoxia and play great roles as "educated cells" in mediating other immune cells, such as DCs. But, the mechanisms how hypoxia affects trophoblastic cells and further modulates the differentiation and function of DCs should be elucidated to clarify local physiological properties. Previous researches have confirmed that some stress conditions such as the exhaust oxygen can induce autophagia which participates in a lot of physiological and pathological processes. In this study, we will exploit GFP-LC3-transfected trophoblast line HTR-8/SVneo, and study the effects and mechamisms of hypoxia on autophagia of trophoblastic cells, then further explore the effect of trophoblast cells autophagia change on the differentiation and functions of DCs from biological and physics characteristics. These studies will further broaden views in implantation and explain the regulations and related mechanisms about differentiation and functions of DCs from

英文关键词： Trophoblasts；hypoxia；autophagy；dendritic cells；MDSCs