医学分子生物学杂志 ›› 2022, Vol. 19 ›› Issue (1): 41-46.doi: 10.3870/j.issn.1672-8009.2022.01.006

• 论著 • 上一篇    下一篇

c-Ski 调控 p38 信号通路在 TGF-β1 介导人冠状动脉内皮细胞内 皮间充质转化中的作用研究 

  

  1. 上海市浦东新区人民医院心内科 上海市, 201200
  • 出版日期:2022-01-31 发布日期:2022-02-25
  • 基金资助:
    上海市浦东新区卫生和计划生育委员会领先人才培养计划 (No. PWR12017-06), 上海市浦东新区科技发展基金 (No. PKJ2017- Y35) 

c-Ski Suppresses the TGF-β1-Induced Endothelial-to-Mesenchymal Transition of HCAECs through Regulating p38 Activation

  • Online:2022-01-31 Published:2022-02-25

摘要: 目的 探索 c-Ski 蛋白在人冠状动脉内皮细胞内皮间充质转化过程中的表达特征及其调控 p38 信 号通路的机制, 为心肌纤维化提供新的预防和治疗的靶点。 方法 以人冠状动脉内皮细胞 ( human coronary artery endothelial cells, HCAECs) 为研究对象, 采用转化生长因子 β1 (transforming growth factor-beta1, TGFβ1) 诱导构建内皮细胞间充质转化模型, 利用实时荧光定量 PCR ( quantitative real-time PCR, Q-PCR)、 蛋 白免疫印迹法检测 c-Ski 和内皮间充质转化相关标志物的表达。 结果 Q-PCR 和 Western 印迹实验结果显 示, c-Ski 表达水平随着 TGF-β1 诱导浓度的增高而显著降低 (P< 0. 05)。 过表达 c-Ski 后, TGF-β1 诱导的 vimentin、 α-SMA 的表达降低, CD31 的表达升高, 表明 TGF-β1 诱导的 HCAECs 细胞内皮间充质转化被抑 制。 p38 选择性抑制剂 SB203580 处理后, HCAECs 细胞内皮间充质转化程度进一步加深; c-Ski 过表达后, p38 通路被激活; p38 选择性抑制剂 SB203580 可一定程度回复 c-Ski 过表达对 TGF-β1 诱导的 HCAECs 细胞 内皮间充质转化的抑制作用 (P< 0. 05)。 结论 c-Ski 可通过调控 p38 信号通路抑制 TGF-β1 介导人冠状动 脉内皮细胞内皮间充质转化。 

关键词: c-Ski, 内皮间充质转化, p38 信号通路, 冠状动脉内皮细胞

Abstract: Objective To investigate the expression of c-Ski and its role in p38 regulation in the endothelial-to-mesenchymal transition ( EndMT) in human coronary artery endothelial cells, which may provide novel targets for prevention and treatment of myocardial fibrosis. Methods The EndMT model was constructed in HCAECs using TGF-β1. The expression of c-Ski and EndMT markers was detected by quantitative real-time PCR and Western blotting. Results c-Ski was down-regulated after TGF-β1 treatment in the HCAECs. Overexpression of c-Ski suppressed TGF-β1-induced EndMT in HCAECs. The overexpression of c-Ski down-regulated the expression of α-SMA and vimentin, and up-regulated the expression of CD31 in TGF-β1-induced HCAECs ( P < 0. 01 ). The treatment with p38 inhibitor SB203580 further promoted TGF-β1-induced-EndMT in HCAECs; p38 signaling was activated after overexpression of c-Ski. Use of p38 inhibitor SB203580 could partially rescue the inhibitory effect of c-Ski overexpression on TGF-β1-induced EndMT in HCAECs. Conclusion c-Ski suppressed the TGF-β1-induced EndMT of HCAECs via regulating p38 activation. 

Key words: c-Ski, endothelial to mesenchymal transition, p38 signaling pathway, human coronary artery endothelial cells 

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