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  • 黄策,王祎龙,刘海亮.生长分化因子-11活性域对老年小鼠认知水平的影响[J].同济大学学报(医学版),2021,42(5):589-596.    [点击复制]
  • HUANG Ce,WANG Yi-long,LIU Hai-liang.Effects of growth differentiation factor-11(GDF11) active domain on cognition of aged mice[J].同济大学学报(医学版),2021,42(5):589-596.   [点击复制]
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生长分化因子-11活性域对老年小鼠认知水平的影响
黄策,王祎龙,刘海亮
0
(同济大学医学院,上海200092; 同济大学附属东方医院再生医学研究所,上海200123)
摘要:
目的探索生长分化因子-11(growth differentiation factor-11, GDF11)活性结构域是否具有延缓衰老,提高老年小鼠认知水平的能力。方法通过质粒转染过表达GDF11的不同结构域;使用转录组测序和加权基因共表达网络分析(weighted gene co-expression network analysis, WGCNA)寻找GDF11活性结构域的调控功能,以及各结构域之间的调控差异;使用流式细胞术检测细胞周期;通过尾静脉高压注射质粒的方法在老年小鼠体内过表达GDF11不同结构域;使用莫里斯水迷宫实验(Morris water maze, MWM)测试过表达GDF11不同结构域后老年小鼠的认知水平。结果WGCNA分析结果显示,GDF11-C端成熟结构域和GDF11-N端结构域共表达模式相似,都激活了氧化磷酸化和细胞周期信号通路。细胞周期实验结果显示,GDF11-C端活性结构域可以减少细胞周期中G1期细胞的比例(P<0.05),增加S期细胞比例。MWM结果显示,GDF11-C端活性域组老年小鼠第1次到达平台的时间显著短于其他组(P<0.05)。结论GDF11活性域可以通过细胞周期和氧化磷酸化信号通路促进细胞的增殖,同时提高老年小鼠的空间记忆和学习能力。
关键词:  再生医学  生长分化因子11  转录组学  衰老
DOI:10.12289/j.issn.1008-0392.21145
投稿时间:2021-04-12
基金项目:国家自然科学基金面上项目(31671539)
Effects of growth differentiation factor-11(GDF11) active domain on cognition of aged mice
HUANG Ce,WANG Yi-long,LIU Hai-liang
(School of Medicine, Tongji University, Shanghai 200092, China; Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200123, China)
Abstract:
ObjectiveTo explore the roles of growth differentiation factor-11(GDF11) active domain to delay senescence and improve cognitive level in aged mice. MethodsDifferent domains of GDF11 were overexpressed by plasmid transfection. Transcriptome sequencing and weighted co-expression network analysis(WGCNA) were used to search for the regulatory functions of GDF11 terminal active domains and the regulatory differences among these domains. Cell cycle was measured by flow cytometry. Different domains of GDF11 were overexpressed in the aged mice by high pressure injection of plasmid through caudal vein. Morris water maze test(MWM) was used to test the cognitive level of mice after expressing different domains of GDF11. ResultsWGCNA analysis showed that the GDF11-C terminal mature domain and GDF11-N terminal co-expression pattern were similar, and both activated oxidative phosphorylation and cell cycle signaling pathways. Flow cytometry revealed that the active domain of GDF11-C terminal reduced the proportion of G1 phase cells(P<0.05) and increased the proportion of S phase cells in the cell cycle. Morris water maze test demonstrated that the first time to reach the platform in GDF11-C terminal active domain group was significantly shorter than that in other groups(P<0.05). ConclusionGDF11 active domain can promote cell proliferation through cell cycle and oxidative phosphorylation signaling pathway, and improve spatial memory and learning ability of the aged mice.
Key words:  regenerative medicine  growth differentiation factor-11  transcriptome  aging

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