梅斯1调节产后心肌细胞细胞循环停止的作用
Ahmed I Mahmoud1, Fatih Kocabas1, Shalini A Muralidhar1
1Department of Internal Medicine, Division of Cardiology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Nature
|April 19, 2013
概括
新生儿的心脏通过心肌细胞的增殖再生,但这种能力在出生后丢失. Meis1 (转录因子) 控制了这种细胞循环,为心脏再生疗法提供了一个目标.
科学领域:
- 心血管生物学 心血管生物学
- 发展生物学 发展生物学
- 分子心脏病学分子心脏病学
背景情况:
- 新生儿哺乳动物的心脏通过心肌细胞增殖表现出显著的再生能力.
- 这种再生能力在出生后的第7天减少,心肌细胞循环停止的机制尚未完全理解.
- 家庭主体转录因子Meis1对于心脏发育至关重要,但其在心肌细胞中的具体作用尚不清楚.
研究的目的:
- 研究Meis1在调节心肌细胞增殖和细胞循环中的作用.
- 为了确定Meis1是否影响心肌细胞再生能力的窗口.
- 探索Meis1作为促进心脏再生的潜在治疗点.
主要方法:
- 在小鼠模型中利用基因操纵在心肌细胞中删除或过度表达Meis1.
- 在不同产后阶段和成人心脏中评估心肌细胞增殖和细胞周期状态.
- 分析了Meis1的转录标,专注于细胞循环抑制剂.
主要成果:
- 心肌细胞中Meis1的缺失延长了产后增殖窗口,并在不损害心脏功能的情况下在成年心肌细胞中重新激活了线粒分裂.
- Meis1的过度表达减少了新生儿心肌细胞的增殖,并抑制了新生儿心脏的再生.
- 发现Meis1对于CDK抑制剂p15,p16和p21的转录激活至关重要.
结论:
- 梅斯1作为心肌细胞增殖的关键转录调节剂.
- Meis1控制心肌细胞的细胞周期退出,从而限制了心脏的再生.
- 向Meis1为增强心脏修复和再生提供了一个潜在的治疗策略.
相关概念视频
01:28The Cell Cycle Control System
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
02:36Cells Coordinate Growth and Proliferation
Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
02:39Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...