CD44连接了血管内皮的自衰退和衰老
Lu Zhang1, Peichang Yang2, Jingxuan Chen2
1College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China. zhanglu@haut.edu.cn.
Nature communications
|September 8, 2023
概括
CD44是一种细胞粘附分子,通过抑制自,驱动血管内皮细胞衰老. 降低CD44水平或激活自可以逆转这些与年龄相关的变化,为血管衰老提供潜在的治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 老年学是指老年学的学科.
背景情况:
- 内皮细胞自衰退与血管衰老和疾病有关.
- 血管内皮细胞 (VEC) 中精确的分子机制尚未完全理解.
研究的目的:
- 研究CD44在VECs中调节自和衰老中的作用.
- 为了阐明连接CD44,自和内皮衰老的分子通路.
主要方法:
- 确定了CD44在VEC自和衰老中的作用.
- 研究了CD44细胞间域 (CD44ICD) 对PIK3R4,PIK3C3和STAT3信号传递的影响.
- 在VEC中利用了CD44敲除和一个内皮特异性的CD44ICD敲进小鼠模型.
- 在过度表达CD44ICD的VEC和具有clec-31的C. elegans中检查了自激活.
主要成果:
- CD44ICD通过降低PIK3R4/PIK3C3水平和破坏STAT3依赖的PtdIns3K复合体来负面调节自.
- 血管内皮中的CD44水平随着年龄的增长而增加,其同类物clec-31在C. elegans中.
- CD44的淘汰改善了与年龄相关的VEC表型.
- CD44ICD试验小鼠显示寿命缩短和VEC过早衰老,自性降低.
- 自活性激活逆转了人类和小鼠VEC中CD44ICD诱导的过早衰老,这种功能在C. elegans中保留.
结论:
- CD44在将自衰退与血管内皮细胞衰老联系起关键作用.
- CD44介导的自调节呈现了一种新的机制,有助于血管衰老.
- 向CD44或增强自可能为抗击血管衰老和相关疾病提供策略.
相关概念视频
Autophagy
4.3K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.3K
Delivery Pathways to the Lysosome
6.6K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.6K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
Mitochondria
13.7K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
13.7K


