通过抑制CEND1通过LSD1调节心脏再生
Huahua Liu1,2, Jinling Dong2, Shuang Liu3
1Department of Cardiology, First Affiliated Hospital; Cardiometabolic Innovation Center of Ministry of Education, Xi'an Jiaotong University, Xi'an, China.
Theranostics
|June 16, 2025
概括
激活LSD1和抑制Cend1促进小鼠在受伤后的心脏再生. 这种表观遗传轴对于修复新生儿和成人心脏损伤至关重要.
科学领域:
- 心血管生物学 心血管生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 再生医学是一种再生医学.
背景情况:
- 重新激活心肌细胞增殖是心脏再生的关键.
- LSD1-CEND1轴在表观遗传上抑制了Cend1,这对心肌细胞增殖和心脏发育至关重要.
研究的目的:
- 研究LSD1-CEND1轴在心脏受伤后的再生和修复中的作用.
- 探索改善心脏修复的治疗策略.
主要方法:
- 使用心肌细胞特异性Lsd1淘汰/过度表达和Cend1无/过度表达的小鼠模型.
- 通过切除 (新生儿) 或冠状动脉结合 (成人) 诱导心脏损伤.
- 评估心脏功能 (心声学) 和组织学 (马森染色);分析分子变化 (RNA-seq,qPCR,西斑,免疫染色).
主要成果:
- Lsd1 缺失影响新生儿心脏再生;Lsd1 过度表达改善了它.
- 作为心肌细胞循环的抑制剂,Cend1在Lsd1损失时被上调.
- 过度表达Cend1阻碍了再生;Cend1的删除促进了再生,增强了心肌细胞的增殖,新血管和巨细胞的激活.
- 由Lsd1损失引起的再生缺陷通过Cend1删除得到了挽救.
- 在成年小鼠中,Lsd1过度表达或Cend1删除改善了心肌梗塞后的心脏功能.
结论:
- 在新生儿和成年小鼠中,对CEND1的LSD1依赖性抑制对心脏再生至关重要.
- 向LSD1激活和CEND1抑制可能为内源性心脏修复提供治疗策略.
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