通过Vldlr,Thrombospondin 1和Reelin作用于调节心脏生长和修复
Lijuan Pei1, Zhaohui Ouyang1, Hongjie Zhang1
1School of Life Sciences and Technology, Institute for Regenerative Medicine, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Shanghai East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, Tongji University, 1239 Siping Road, Shanghai, 200092, China.
非常低密度脂蛋白受体 (Vldlr) 信号抑制心肌细胞的增殖,阻碍心脏的修复. 针对这种途径可能会改善受伤后的心脏再生.
科学领域:
- 心血管生物学 心血管生物学
- 再生医学是一种再生医学.
- 分子信号传输的方法
背景情况:
- 成年心肌细胞在受伤后表现出有限的再生能力,影响心脏的修复.
- 抑制心肌细胞增殖的细胞外信号在很大程度上是未知的.
- 了解这些信号对于开发心脏再生疗法至关重要.
研究的目的:
- 为了识别调节心肌细胞细胞循环的细胞外信号.
- 阐明非常低密度脂蛋白受体 (Vldlr) 在心肌细胞增殖中的作用.
- 调查Vldlr信号对心脏再生的影响.
主要方法:
- 在产后心肌细胞中受体的剖析.
- 研究Vldlr连接体 (Reelin和Thrombospondin1) 对心肌细胞增殖的影响.
- 使用具有向基因删除 (Reln,Thbs1,Vldlr) 和心肌梗塞的遗传小鼠模型.
- 分析下游的信号通路,包括Rac1和Yap.
主要成果:
- Vldlr 抑制新生儿心肌细胞细胞循环的增殖.
- 里林促进增殖,而Thrombospondin1 (TSP-1) 通过Vldlr.抑制它.
- TSP-1/Vldlr信号通过Rac1和Yap调节心肌细胞循环.
- 对Vldlr或TSP-1的遗传干扰增强了心肌细胞的增殖和心脏的修复.
- 雷伦缺乏会影响新生儿心肌细胞的增殖和再生.
结论:
- Vldlr集成了细胞外信号来控制心肌细胞循环和存活.
- 抑制TSP-1-Vldlr轴有助于成人哺乳动物心脏修复能力有限.
- 准Vldlr信号提供了增强心脏再生的潜在治疗策略.
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