GRP94通过PI3K/AKT/mTOR信号通路促进牛肌肉卫星细胞分化  

GRP94 promotes differentiation of bovine skeletal muscle satellite cells through PI3K/AKT/mTOR signaling pathway

作　　者：李爽[1,2] 付玉莹 佟慧丽 李树峰[1,2] 严云勤 LI Shuang;FU Yuying;TONG Huili;LI Shufeng;YAN Yunqin(College of Life Science,Northeast Agricultural University,Harbin 150030,China;Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province,Harbin 150030,China)

机构地区：[1]东北农业大学生命科学学院细胞与发育生物学实验室,黑龙江哈尔滨150030 [2]黑龙江省动物细胞与基因工程重点实验室,黑龙江哈尔滨150030

出　　处：《中国兽医学报》2023年第10期2101-2108,共8页Chinese Journal of Veterinary Science

基　　金：国家自然科学基金青年基金资助项目(31801150);东农学者青年才俊资助项目(20QC22);东农学者学术骨干资助项目(20XG10)。

摘　　要：葡萄糖调节蛋白94(glucose-regulated protein 94,GRP94)对骨骼肌的发育至关重要,但其对牛肌肉卫星细胞(muscle derived satellite cells,MDSCs)分化的影响及作用机制尚未见报道。本试验检测GRP94在牛MDSCs分化过程中的表达情况;采用CRISPR基因编辑技术调控GRP94表达,检测GRP94对肌肉分化标志基因myogenin(MyoG)、myosin heavy chain(MHC)的表达及肌管融合率的影响;分别添加PI3K和mTOR的抑制剂明确PI3K信号通路对牛MDSCs分化的影响;检测GRP94对PI3K/AKT/mTOR信号通路活性的影响。GRP94随着牛MDSCs分化表达逐渐上调,GRP94正向调控牛MDSCs分化。PI3K信号通路抑制牛MDSCs分化,GRP94负调控PI3K/AKT/mTOR信号通路的活性。综上,本试验阐明了GRP94通过抑制PI3K/AKT/mTOR信号通路促进牛MDSCs分化的分子机制,为肉牛育种以及肉质改善提供了重要的理论支持。Glucose-regulated protein 94(GRP94)is essential for skeletal muscle development,but its effect and mechanism on the differentiation of bovine skeletal muscle satellite cells(MDSCs)have not been reported.In this study,the expression of GRP94 was detected during differentiation of bovine MDSCs.Using CRISPR gene editing technology to regulate the expression of GRP94,the effect of GRP94 on expression of MyoG,MHC and myotube fusion rate were detected.The inhibitors of PI3K and mTOR were added to clarify the differentiation of bovine MDSCs impacted by PI3K signaling pathway.The effect of GRP94 on the activity of PI3K/AKT/mTOR signaling pathway was detected.The results showed that the expression of GRP94 increased with the differentiation of bovine MDSCs;GRP94 positively regulated the differentiation of bovine MDSCs;PI3K signaling pathway inhibited the differentiation of bovine MDSCs.GRP94 negatively regulated the activity of PI3K/AKT/mTOR signaling pathway.In conclusion,this study clarifies that GRP94 promotes the differentiation of bovine MDSCs by inhibiting the PI3K/AKT/mTOR signaling pathway,which provides important theoretical support for beef cattle breeding and meat quality improvement.

关 键 词：牛 肌肉卫星细胞 细胞分化 GRP94 

分 类 号：Q291[生物学—细胞生物学]