索克斯10通过调解血管光滑肌肉细胞转分化和新极端增生症中 pyroptosis 来升级血管炎症
Xin Xu1, Dan-Dan Zhang1, Peng Kong1
1Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China.
血管光滑肌细胞转化为巨类细胞,导致血管增生. Sox10乳化促进了这一过程,为治疗血管炎症和动脉样硬化并发症提供了潜在的点.
科学领域:
- 心血管生物学 心血管生物学
- 细胞生物学 细胞生物学
- 炎症研究 炎症研究
背景情况:
- 血管光滑肌细胞 (VSMCs) 在持续的炎症损伤期间可以经历转化为巨类细胞的转化.
- 这种细胞可塑性有助于血管增生和动脉样硬化并发症.
- 巨类VSMC被确定为小鼠新极端增生症中的关键细胞群.
研究的目的:
- 研究与性别决定区域Y (SRY) 相关的HMG-box基因10 (Sox10) 在VSMC转差和血管炎症中的作用.
- 阐明Sox10调节VSMC可塑性和热的分子机制.
- 探索针对Sox10在与炎症相关的血管疾病中的治疗潜力.
主要方法:
- 单细胞RNA测序以确定新极端增生症中关键细胞群.
- 实验室内研究,以检查Sox10乳化及其通过瘤缩因子α (TNF-α) 和PI3K/AKT信号的调节.
- 使用RGS5淘汰赛小鼠进行体内研究,以评估Sox10沉默对血管炎症和增生的影响.
主要成果:
- Sox10的上调与巨类的VSMC积累和体外和体外活体中灭有关.
- 通过PI3K/AKT信号传递,TNF-α诱导Sox10乳酸化,促进VSMC转基因差异化和热.
- 调节G蛋白信号传递5 (RGS5) 抑制PI3K/AKT信号传递和Sox10酸化.
- 在RGS5淘汰赛小鼠中,Sox10静音降低了血管炎症和新极度增生症.
结论:
- 索克斯10是VSMC转基因分化,血管炎症和热的关键调节剂.
- 由TNF-α和PI3K/AKT信号调节的Sox10乳化驱动这些病理过程.
- 向Sox10代表了管理诸如动脉样硬化等与炎症相关的血管疾病的潜在治疗策略.
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