纤维肌蛋白依赖的整合蛋白信号传递驱动了血管光滑肌细胞中的EphA2表达
Brenna Pearson-Gallion1,2, Alexandra C Finney3,2, Matthew L Scott2
1Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, Louisiana, United States.
通过整合素传递的纤维菌素信号激活NF-κB,驱动EphA2受体在血管光滑肌细胞中的氨酸激酶表达. 抑制整合素可以降低动脉样硬化斑块中的EphA2.
科学领域:
- 血管生物学和细胞信号传递
- 动脉样硬化病原体的产生
- 受体氨酸激酶调节受体氨酸激酶调节
背景情况:
- 血管光滑肌细胞 (VSMCs) 在动脉样硬化中转变为合成表型,增加增殖和矩阵沉积.
- 在合成的VSMC和动脉样硬化斑块中,EphA2受体氨酸激酶被上调.
- 调节VSMC EphA2表达的机制在很大程度上是未知的.
研究的目的:
- 阐明调节血管光滑肌细胞中EphA2表达的信号通路.
- 调查纤维素和整合素信号传导在EphA2诱导中的作用.
- 确定抑制这些通路对动脉样硬化的影响.
主要方法:
- 用血清,生长因子和纤维菌素刺激的VSMC进行细胞培养研究.
- 在体外和体内抑制纤维素-整合素相互作用和NF-κB信号传递.
- RNA测序以识别纤维内克反应基因.
- 染色体免疫沉以评估NF-κB与EphA2促进体的结合.
- 在ApoE淘汰赛小鼠中的动脉样硬化斑块分析.
主要成果:
- 粘附于纤维素,而不是生长因子,刺激了VSMC中的EphA2表达.
- 阻断纤维素-整合素相互作用在体外和体内减弱了EphA2的表达.
- RNA测序确定NF-κB是纤维素蛋白诱导基因表达的关键媒介.
- 纤维肌菌素增强了NF-κB激活,直接与EphA2促进体结合.
- 抑制NF-κB或整合素减少了动脉样硬化斑块中的EphA2表达.
结论:
- 纤维菌素依赖整体蛋白信号传递是一种新的机制,可诱导VSMC中的EphA2表达.
- NF-κB作为一个关键的转录因子,将纤维素-整蛋白信号与EphA2上调相关联.
- 向纤维素-整合素-NF-κB-EphA2轴可能为动脉样硬化提供治疗策略.
- 对EphA2的矩阵特异性调节对其他病理状况有更广泛的影响.
更多相关视频
09:10Human Saphenous Vein Endothelial Cell Isolation and Exposure to Controlled Levels of Shear Stress and Stretch
Published on: April 21, 2023
11:56In vitro Method to Observe E-selectin-mediated Interactions Between Prostate Circulating Tumor Cells Derived From Patients and Human Endothelial Cells
Published on: May 15, 2014
相关概念视频
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Intracellular Signaling Affects Focal Adhesions
Some...
Fibronectins Connect Cells with ECM
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
Regulation of Angiogenesis and Blood Supply
Integrins
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Activation of Integrins
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...
