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外体微RNA转移到巨细胞中介细胞后调节
Geoffrey de Couto1, Romain Gallet1, Linda Cambier1
1From Cedars-Sinai Heart Institute, Los Angeles, CA (G.d.C., R.G., L.C., E.J., N.M., J.F.D., B.P.B., E.M.); and Cedars-Sinai Center for Bioinformatics and Functional Genomics, Los Angeles, CA (B.P.B.).
Circulation
|April 16, 2017
概括
通过重编程巨细胞来减少心脏病发作的损伤. 外体miR-181b通过向PKCδ来调解这种作用,为心肌梗塞提供了一种新的治疗策略.
科学领域:
- 心血管生物学
- 细胞疗法
- 外体生物学
背景情况:
- 在急性心肌梗塞中,心脏球衍生细胞 (CDC) 通过巨分化保护心脏.
- 疾病预防控制中心分泌的外体 (CDCexo) 正在研究其复制疾病预防控制中心治疗的心脏保护作用的潜力,称为细胞后调节.
研究的目的:
- 确定CDC分泌的外体细胞 (CDCexo) 是否可以在心肌梗塞中复制心脏球衍生细胞 (CDC) 的心脏保护作用.
- 阐明潜在的分子机制,特别是微RNA (miRNA) 和巨分离的作用.
主要方法:
- 在大鼠和猪模型中通过缺血/再输血诱导心肌梗塞.
- 进行了冠内输注的CDCexo,纤维细胞外体 (Fbexo) 或载体.
- 分析了心脏病发作的大小,巨细胞群 (CD68+),Mφ两极分化,外体miRNA含量和Mφ基因表达特征 (RNA测序).
主要成果:
- 与Fbexo不同的是,CDCexo在老鼠和猪模型中显著降低了心脏病的大小.
- 在心脏病发作的组织中降低了CD68+Mφ,改变了Mφ极化.
- 在CDCexo中,miR-181b被确定为Mφ两极分化的关键媒介,准PKCδ;用miR-181b设计的Fbexo模仿了这些效应.
结论:
- 从疾病预防控制中心向巨细胞的miR- 181b外体转移是转血后观察到的心脏保护作用的基础.
- 这种机制涉及PKCδ转录水平的降低,突出了心肌梗塞治疗的新疗法.
相关概念视频
MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...

