Sox9通过调节细胞外基质组成和度来加速血管衰老
Maria Faleeva1, Sadia Ahmad1, Konstantinos Theofilatos1
1British Heart Foundation (BHF) Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences (M.F., S.A., K.T., G.W., M.W., C.M.S.) King's College London, United Kingdom.
细胞衰老和硬化的细胞外基质 (ECM) 促进Sox9的表达,这推动了进一步的ECM修饰,加速了血管衰老. 这项研究揭示了血管衰老中的反周期.
科学领域:
- 血管生物学 血管生物学
- 细胞衰老 细胞衰老
- 生物材料科学 生物材料科学
背景情况:
- 血管化和细胞外矩阵 (ECM) 刚度的增加是血管衰老的关键特征.
- Sox9 (SRY-box转录因子9) 与血管光滑肌细胞 (VSMC) 骨/肌转化有关,但其在衰老和化中的作用尚不清楚.
研究的目的:
- 研究Sox9,血管衰老和ECM特性之间的关系.
- 阐明Sox9在调节老化过程中的VSMC表型和ECM特征中的作用.
主要方法:
- 从年轻和老年患者的人类大动脉样本上的免疫组织化学.
- 在体外研究中使用年轻和老化的VSMC,操纵Sox9表达.
- 使用原子力显微镜和蛋白质组学对ECM属性的表征.
- 在工程矩阵上评估VSMC表型.
主要成果:
- Sox9在体内与衰老标志物p16相关,并在体内在衰老细胞和刚性基质中表现出机械敏感性表达.
- Sox9通过改变原表达和减少VSMC收缩性来调节ECM的刚性和组织.
- 索克斯9向LH3 (前原-氨酸,2-酸酸-5-二氧化原酶3),这是ECM刚性的关键调节器,并通过细胞外囊泡促进其沉积.
结论:
- Sox9在调节ECM结构和组成方面发挥着至关重要的作用,影响VSMC表型.
- 在老化和ECM硬化促进Sox9的地方存在一个积极的反循环,这进一步增强了硬化和老化.
- 研究结果强调了ECM在调节VSMC表型方面的重要性,并建议治疗血管衰老的治疗点.
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