循环RNAcircZFPM2调节心肌细胞缩和存活时间
Dimyana Neufeldt1, Arne Schmidt1,2, Elisa Mohr1
1Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany.
Basic research in cardiology
|April 19, 2024
概括
像circZFPM2这样的循环RNA (circRNAs) 显示出对治疗多变性心肌病 (HCM) 的前景. 这项研究发现circZFPM2保护心脏细胞并改善这种遗传性心脏疾病模型中的功能.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 心脏病学 心脏病学
背景情况:
- 增高性心肌病变 (HCM) 是最常见的遗传性心脏病.
- 目前对HCM的治疗方法在很大程度上是症状性的,并不能完全解决分子原因.
- 循环RNAs (circRNAs) 正在成为细胞功能的关键调节者.
研究的目的:
- 为了确定HCM治疗的新型分子标.
- 调查circRNAs在HCM病变发生中的作用.
- 评估circZFPM2作为心脏缩的潜在治疗剂.
主要方法:
- 全球circRNA在人类心脏组织中特定的下一代测序.
- 在新生小鼠和人类诱导的多能干细胞干细胞衍生的心肌细胞 (hiPSC-CMs) 中进行了体外功能丧失和功能获取研究.
- 评估心肌细胞功能,线粒体呼吸,亡和基因表达.
- 在体内研究使用HCM患者衍生心脏器官和Multi-Omics分析.
主要成果:
- 确定circZFPM2 (hsa_circ_0003380) 是一个高度保守的circRNA,在HCM心脏组织中显著上调.
- 敲击circZFPM2诱导心肌细胞增大,线粒体呼吸功能受损,活性氧物种增加,并促进了亡.
- 通过脂质纳米颗粒或AAV载体,circZFPM2的过度表达,挽救了多变性基因表达和增强了细胞存活率.
- 在HCM衍生的心脏器官中,CM特定的circZFPM2过度表达改善了收缩性和线粒体功能.
结论:
- circZFPM2对心脏缩和功能障碍起着保护作用.
- circZFPM2显示出作为HCM和其他心脏缩条件的新疗法标的潜力.
- 传递circZFPM2为治疗遗传性心脏疾病提供了一个有希望的策略.
相关概念视频
Formation of Muscle Fibers from Myoblasts
4.9K
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
4.9K
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K


