通过长非编码RNA-H19调节心脏中的新肌细胞形成
Vagner Oliveira Carvalho Rigaud1, Robert C Hoy1, Justin Kurian1
1Center for Metabolic Disease Research (V.0.C.R., R.C.H., J.K., C.Z., M.B., I.B., J.P., T.P., M.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Circulation
|October 31, 2022
概括
在单核双胞胎心肌细胞中,RNA结合蛋白LIN28a重编程新陈代谢,促进其持久性,并增强受伤后的心脏修复. 这一发现将心肌细胞代谢与心脏的调节和再生联系在一起.
科学领域:
- 心血管生物学
- 复原医学
- 分子新陈代谢
背景情况:
- 由于心肌细胞周期的退出和多重化,成熟的心脏的再生能力有限.
- 心肌细胞的新陈代谢在出生后发生变化,与再生潜力的丧失相吻合.
- 代谢重编程在维持再生心肌细胞群中的作用尚不清楚.
研究的目的:
- 研究RNA结合蛋白LIN28a在心脏修复中的作用.
- 确定LIN28a是否能够维持单核双胞胎心肌细胞的再生.
- 将新陈代谢重编程与心肌病和心脏再生联系起来.
主要方法:
- 在小鼠模型中的LIN28a过度表达 (转基因,新生儿/成年细胞培养,心肌损伤模型).
- 评估心肌细胞数量,细胞循环状态和性.
- 在LIN28a过度表达心肌细胞中进行代谢分析 (糖分解,ATP产生,酶水平).
- 通过RNA免疫沉测序来识别LIN28a的点.
主要成果:
- 在产后心脏中LIN28a过度表达减少了多体化和增加了心肌细胞循环活性.
- 在年轻小鼠和成年小鼠中改善心脏功能和伤害后的存活率.
- LIN28a增加了心肌细胞的糖解和ATP产生,长非编码RNA- H19被确定为关键点.
- 抑制LIN28a或H19会减弱这些疗效.
结论:
- LIN28a重新编程心肌细胞代谢,促进单核双胞胎细胞的持久性.
- 这种新陈代谢重编程可以改善心脏受伤后的修复和功能.
- LIN28a与心肌细胞代谢和心脏再生过程的调节有关.
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