Gɑi2介导的信号通路在维持咀嚼肌代谢中的作用机制

项目名称： Gɑi2介导的信号通路在维持咀嚼肌代谢中的作用机制

项目编号： No.81200811

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 刘志坚

作者单位： 武汉大学

项目金额： 23万元

中文摘要： 适宜的咀嚼肌形态和功能，既在青少年期引导着牙颌面的正常发育和生长，还在成年期参与下颌功能运动和维持口颌系统的稳定。以往研究提示 G蛋白及其偶联受体(GPCRs)通过对肌肥大（hypertrophy）和肌萎缩(atrophy)相关通路的调节，在躯干骨骼肌代谢中发挥了重要作用。同时也有证据表明咀嚼肌在胚胎来源、代谢机制、生长调控基因等方面有别于躯干骨骼肌。目前对Gαi2相关通路在咀嚼肌代谢中的作用知之甚少。本研究拟通过形态学、分子生物学和动物模型研究方法，探讨1）Gαi2信号通路对咀嚼肌肌管细胞形态的影响；2）Gαi2在咀嚼肌代谢中对肌肥大通路PKC-GSK3β和PI3K-mTor-p70s6K,以及肌萎缩相关信号的调控作用；3）Gαi2对咀嚼肌肌管细胞分化和生长的作用；4）合干扰动物模型中Gαi2对咀嚼肌肌纤维合成和生长的可能作用，揭示Gαi2介导的信号通路在维持咀嚼肌代谢中的可能作用机制。

中文关键词： Gαi2；咀嚼肌肌卫星细胞；激活；增殖；分化

英文摘要： Optimal form and function of masticatory muscles is believed as not only an important factors in mandibular movement and in stablizing the whole gnathostomatic system, but also guides the normal development and growth of dentofacial structures. Previous studis suggested that G-protein (guanine mucleotide-binding proteins)and its receptors (GPCRs) may play a pivotal role in the metabolism of trunk skeletal muscles. Numerous reliable research evidences also revealed that masticatory muscles is significantly different from trunk skeletal muscles since its unique characters in embryological origins, metabolic signal networks and myogenesis regulating genes. Currently there is still a lack of knowledge on the potential role of Gαi2 mediated pathways in regulating masticatory muscle metabolisms. This study is to claify the potential role of Gαi2 in mediating masticatory muscle metabolism by 1)investigating the effect of Gαi2-mediated signaling on myotube cell morphology; 2)exploring the molecular biological mechanism of Gαi2 pathways in masticatory muscle metabolism, especially to explore its potential role in muscular hypertrophy pathways (PKC-GSK3βpathway ; PI3K-mTor-p70s6K pathway)and in muscular atrophy pathways (TNF-α-MuRF1-MAFbx) ; 3）oberving the effect of Gαi2 on the differentiation and maturation of myotube c

英文关键词： Gαi2；masticatory muscle satellite cells；activation；proliferation；differentiation