调节单细胞/巨细胞等离子体激活剂活性表达的表达及其对减弱血管病变的影响
C H Lundgren1, H Sawa, B E Sobel
1Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110.
Circulation
|October 1, 1994
概括
转化生长因子-β和血栓激素在单细胞中增加尿素酶激素激活因子受体 (uPAR) 和激素激活因子抑制剂-1 (PAI-1),可能影响动脉样硬化和复原.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 心血管研究的心血管研究.
背景情况:
- 结合其受体 (uPAR) 的细胞表面尿素酶类型等离子素激活剂 (uPA) 可以影响细胞外基质 (ECM) 降解.
- 在单细胞/巨细胞上,uPA与等离子体激活因子抑制剂 (PAI-1和PAI-2) 的相互作用可能通过改变蛋白质分解活性,ECM降解和新极形形成来影响动脉生成.
研究的目的:
- 研究人类单细胞中与纤维解析相关的细胞表面蛋白质表达的变化.
- 确定转化生长因子-β (TGF-β) 和血栓对U937单细胞样细胞的影响.
主要方法:
- U937细胞暴露于TGF-β和血栓.
- 对UPAR,PAI-1和PAI-2的基因和蛋白质表达进行了分析,使用mRNA分析,蛋白质合成试验和代谢标记.
- 在人类冠状动脉切除标本上使用了免疫组织化学和现场杂交.
主要成果:
- TGF-β和血诱导了UPAR mRNA和增加了细胞表面的蛋白质分解活性.
- 氨酸增加了PAI-2 mRNA,而TGF-β抑制了它.
- TGF-β诱导了PAI-1 mRNA和蛋白质以时间依赖的方式,这些发现反映在人类动脉瘤样本中.
- PAI-1和UPAR被局部化到单细胞/巨细胞和动脉瘤中的光滑肌细胞.
结论:
- 在单细胞中,TGF-β和血诱导PAI-1和UPAR.
- 这些过程可能在单细胞迁移和瘤中ECM蛋白解中发挥作用.
- 单细胞中的细胞表面纤维解可能会影响动脉样硬化和复原.
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