三素53通过调节焦点粘附周转和尖端细胞形成来抑制血管生成
Shuangshuang Yuan1,2, Qin Yu1, Tangting Chen3
1Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Luzhou Municipal Key Laboratory of Thrombosis and Vascular Biology, Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.
Journal of cellular and molecular medicine
|February 24, 2025
概括
复合人体密苏古53 (rhMG53) 通过洞穴和克拉特林依赖的通路进入内皮细胞,通过减少焦点粘附周转率和尖端细胞形成来抑制血管生成.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 三古53 (MG53) 是一种新的血管生成调节剂.
- 细胞吸收机制和MG53的细胞运动调解仍然在很大程度上未知.
研究的目的:
- 阐明细胞内皮细胞中复合人MG53 (rhMG53) 的细胞吸收机制.
- 研究rhMG53如何调节内皮细胞功能和迁移.
- 评估rhMG53在抑制过度血管生成方面的治疗潜力.
主要方法:
- 通过使用caveolin-1 knockdown和pitstop-2 (clathrin 抑制剂) 调查 rhMG53 的吸收.
- 评估了rhMG53对焦粘附激酶 (FAK) 和帕克西林酸化的影响.
- 利用3D原培养模型来分析尖端细胞的形成和管形成.
- 在体内评估了rhMG53在预防角膜新血管化的有效性.
主要成果:
- rhMG53的吸收取决于洞穴和克拉特林介导的内细胞分裂.
- 内部化rhMG53抑制FAK和帕克西林酸化,减少焦点粘附周转率.
- rhMG53在体外显著抑制尖端细胞的形成和管形成.
- rhMG53在体内有性损伤后有效防止角膜新血管化.
结论:
- rhMG53通过调节焦点粘附周转和尖端细胞形成来抑制血管生成.
- 这项研究揭示了rhMG53细胞吸收和功能的新机制.
- rhMG53显示出作为治疗过度血管生成特征的疾病的治疗剂的潜力.
相关概念视频
01:24Regulation 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
01:10Mechanism of Angiogenesis
5.2K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
5.2K
01:17Intracellular Signaling Affects Focal Adhesions
2.5K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.5K
01:24Overview of Cell-Matrix Interactions
7.0K
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
7.0K
01:15Activation of Integrins
3.2K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.2K
02:38Mitogens and the Cell Cycle
6.4K
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...
6.4K