肺损伤诱导的激活内皮细胞状态在与衰老相关的渐进性纤维化中持续存在
Ahmed A Raslan1,2,3, Tho X Pham1,2, Jisu Lee1
1Arthritis and Autoimmune Diseases Center, Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
Nature communications
|June 27, 2024
概括
衰老会通过导致持续的内皮细胞激活来损害肺部的修复,从而阻碍纤维化后的恢复. 这种与YAP/TAZ活性相关的功能障碍在老年肺部更为明显,影响血管健康.
科学领域:
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
- 肺部医学 肺部医学
背景情况:
- 渐进性肺纤维化与与衰老相关的内皮细胞功能障碍有关.
- 肺纤维化中内皮细胞变化的具体机制尚不清楚.
研究的目的:
- 为了研究肺纤维化年轻小鼠与老年小鼠的内皮细胞变化.
- 了解YAP/TAZ信号在内皮细胞激活和肺部修复中的作用.
主要方法:
- 单细胞RNA测序的白素受伤的小鼠肺部 (年轻和老年).
- 血统追踪可以追踪随时间推移内皮细胞激活动态.
- 在体外实验中评估YAP/TAZ和BDNF对内皮细胞的影响.
主要成果:
- 在ACKR1+静脉和TrkB+毛细血管细胞中发现了激活的内皮细胞状态 (低氧,糖解,YAP/TAZ).
- 与年轻小鼠相比,老年小鼠的内皮细胞活化更为普遍和持久.
- 在激活的肺内皮细胞中看到的YAP/TAZ激活在体外诱导基因,并与BDNF合作促进毛细血管形态发生.
结论:
- 老年肺部持续的内皮细胞激活有助于损伤修复和纤维化.
- 在衰老和纤维化中,YAP/TAZ信号传递在内皮细胞激活和血管功能障碍中起着至关重要的作用.
- 准YAP/TAZ和BDNF通路可能为肺纤维化提供治疗策略.
相关概念视频
Regulation of Angiogenesis and Blood Supply
2.5K
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...
2.5K
Liver Regeneration
3.2K
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
3.2K
Introduction to Fibroblasts
3.1K
Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
3.1K


