Ghrelin抑制胸腺脂肪细胞生成的分子调控网络研究

项目名称： Ghrelin抑制胸腺脂肪细胞生成的分子调控网络研究

项目编号： No.31272519

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 农业科学

项目作者： 李玉谷

作者单位： 华南农业大学

项目金额： 81万元

中文摘要： 胸腺脂肪性退化导致T细胞产量和免疫力下降。前期研究表明Ghrelin能够抑制胸腺脂肪细胞生成，但其分子机理尚未阐明。本项目拟通过小鼠体内注射Ghrelin、体外诱导胸腺间充质干细胞分化为脂肪细胞过程中添加Ghrelin、构建过表达Ghrelin的胸腺间充质干细胞模型及采用RNAi阻断相关信号通路分子表达后，应用荧光定量PCR、蛋白质印迹和基因芯片技术研究Ghrelin对脂肪细胞生成相关的信号转导分子、转录因子、转录辅助因子、microRNAs和脂肪细胞特异标志物表达的影响；从而阐明Ghrelin抑制胸腺脂肪细胞生成的分子调控网络，揭示胸腺脂肪性退化的调控机理；为临床应用Ghrelin作为免疫增强剂抑制胸腺退化或促进其再生奠定理论基础，开辟增强或恢复胸腺免疫功能的新思路和新策略，并为人类和伴侣动物的肥胖症等能量代谢综合征寻找新的治疗靶标以及调控家畜的脂肪组织发育从而改善肉质等提供借鉴和参考。

中文关键词： Ghrelin；胸腺退化；脂肪细胞生成；间充质干细胞；microRNAs(miRNAs)

英文摘要： Adipose-related thymic involution results in a progressively decline in T cell output and immunity. Previous studies have showed that ghrelin can suppress thymic adipogenesis, but the molecular mechanisms have not yet been clear. In order to elucidate the regulatory mechanisms underlieing thymic adiposity and molecular regulatory network involved in ghrelin suppressing thymic adipogenesis, this work aims to investigate the effects of ghrelin on expression of adipogenesis-related signal transduction elements, transcription factors, transcriptional cofactors (coactivators and corepressors), microRNAs(miRNAs) and adipocyte-specific markers in thymus after intraperitoneally administration of ghrelin to mice and during induced differentiation of thymic mesenchymal stem cells to adipocytes after administration of ghrelin in vitro, and constructing thymic mesenchymal stem cells overexpressing ghrelin and blocking related signal pathway molecules via RNA interference by real time-PCR, western blot, miRNAs microarray assay. It means to establish a foundation for ghrelin as an immunopotentiator clinically to suppress thymic involution or to promote its regeneration, developing novel ideas and strategies for strengthening or recovering thymic immune function, and to provide a useful guidance for questing new appropriate th

英文关键词： Ghrelin；thymus involution；adipogenesis；mesenchymal stem cells；microRNAs(miRNAs)