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补充受体C5aR1在成功的心脏再生中发挥着进化保存的作用
Niranjana Natarajan1, Yamen Abbas1, Donald M Bryant1,2,3
1Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA (N.N., Y.A., D.M.B., A.U., L.H.C.-D., N.N.H., J.L.W., R.T.L.).
Circulation
|January 20, 2018
概括
研究跨物种的心脏再生表明,激活5a受体1促进心肌细胞在心脏受伤后的增殖,为成功的心脏修复机制提供了洞察力.
科学领域:
- 心血管生物学
- 复原医学
- 比较基因组学
背景情况:
- 成年哺乳动物在受伤后心脏再生有限.
- 了解动物模型中保存的分子通路是解锁哺乳动物心脏修复的关键.
- 早期再生的转录组分析可以阐明进化保存的途径.
研究的目的:
- 进行跨物种转录性查以检查心脏再生.
- 为了确定心脏修复所涉及的保存分子通路.
- 研究特定免疫路径在心肌细胞增殖中的作用.
主要方法:
- 在受伤后对鱼,新生小鼠和斑马鱼心脏进行比较的转录组分析.
- 在尖端切除后12,24和48小时进行RNA测序 (10-20%的心室质量去除).
- 使用抑制和遗传删除对5a受体1 (C5aR1) 的功能评估.
主要成果:
- 包括补充受体在内的炎症和补充通路基因的升高调节在不同物种中被观察到.
- 在再生的心脏中诱导补充5a受体1 (C5aR1) 表达.
- 在心脏损伤后抑制或遗传删除C5aR1显著降低了心肌细胞的增殖.
结论:
- 补充5a受体1的激活是一种在心脏损伤后促进心肌细胞增殖的进化保护机制.
- 补充通路的激活是成功心脏再生的关键通路.
- 准补充路径有可能改善心脏的修复.
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