SIRT1调控Wnt信号通路影响间充质干细胞成脂定向的机制

项目名称： SIRT1调控Wnt信号通路影响间充质干细胞成脂定向的机制

项目编号： No.31272457

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： 彭健

作者单位： 华中农业大学

项目金额： 80万元

中文摘要： 干细胞的定向分化由复杂的调控网络控制，涉及多个功能基因开启与关闭。Wnt是控制干细胞成脂的关键信号，但在此过程中Wnt信号受调控的机制尚不清楚。本研究在前期研究基础上提出的假设是：在间充质干细胞的命运决定中，SIRT1可能通过调控Wnt通路拮抗物来影响Wnt信号，并决定间充质干细胞的成脂定向。拟以鼠C3H10T1/2细胞为材料，采用细胞培养结合RNAi与过表达、荧光素酶报告系统、qPCR、western-blot和ChiP等技术，研究SIRT1①是否调控间充质干细胞成脂定型和分化；②是否通过影响Wnt信号通路来调控；③在调控中是否通过Wnt通路拮抗物来作用；以及④阐明调控Wnt通路拮抗物的分子机制。本项目通过构建SIRT1调控间充质干细胞定向为脂肪细胞的信号传导网络，并阐明间充质干细胞成脂定向的分子机制，对揭示动物胴体脂肪沉积、肌内脂肪形成和人类肥胖相关疾病的产生机理，具有重要意义。

中文关键词： 间充质干细胞；脂肪生成；SIRT1；Wnt信号通路拮抗物；β-catenin

英文摘要： Stem cell commitment to certain lineage is governed by multiple regulatory networks, which involve activation/inhibition of multiple functional genes. Wnt signaling is a molecular switch that governs adipogenesis, however, the underlying mecanism of how Wnt singaling is regulated remains to be investigated.Based on previous research, the present study proposes that SIRT1 regulates Wnt signaling through its antagonists and influences mesenchymal stem cells(MSCs) commitment to adipocyte lineage. By means of cell culture,RNAi, overexpression, luciferase reporting system, qPCR, western blot and ChIP assay, mouse C3H10T1/2 MSCs cell line is employed to determine:①Whether SIRT1 regulates MSCs commitment to adipocyte lineage,②Whether SIRT1 regulation of adipogenic commitment through Wnt signaling,③Whether SIRT1 regulation of adipogenic commitment through regulating Wnt signaling antagonists,and ④Elucidating the molecular mechanism underlying adipogenic commitment of MSCs by SIRT1 through regulation of Wnt signaling antagonists. By investigating the regulatory network of MSCs commitment to adipocyte lineage, understand mechanism of SIRT1 induced MSCs commiment to adipocyte lineage. The present study is of significant importance to elucidating MSCs commiment to adipocyte lineage, fat deposition and intramuscular fat for

英文关键词： mesenchymal stem cells；adipogenesis；SIRT1；Wnt signaling antagonists；β-catenin