间充质干细胞来源的外泌体通过TGF-β1/Smad2/3信号通路抑制高糖诱导的成纤维细胞转分化

被引:21
作者
兰蓓蓓 [1 ]
王娟娟 [1 ]
邵联波 [1 ]
张瑜 [1 ]
周进 [2 ]
孟庆友 [2 ]
韩超珊 [1 ]
朱宝 [1 ]
张鲁鲁 [1 ]
王燕丽 [1 ]
张雨晴 [1 ]
李杨欣 [1 ]
机构
[1] 苏州大学心血管病研究所
[2] 苏州大学附属第一医院
关键词
成纤维细胞; 纤维化; TGF-β1; 高糖; Smad2/3; 外泌体;
D O I
暂无
中图分类号
R587.2 [糖尿病性昏迷及其他并发症];
学科分类号
100201 [内科学];
摘要
心脏纤维化是糖尿病患者心肌功能障碍的主要原因。成纤维细胞转分化为成肌纤维细胞是心脏纤维化过程中的一个关键性事件。该研究的目的是探究高糖诱导成纤维细胞转分化的分子机制,并找寻抑制成纤维细胞转分化的方法。结果显示,经高糖处理的BJ细胞(人皮肤成纤维细胞系)与正常BJ细胞相比,α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的表达明显上调。通过使用SB525334或转化生长因子-β1(transforming growth factor-β1,TGF-β1)si RNA抑制TGF-β1/Smad2/3信号通路的活化,发现α-SMA和胶原I的蛋白质水平及Smad2/3的磷酸化水平均降低。同时,SB525334也抑制了高糖诱导的BJ细胞增殖。大鼠骨髓间充质干细胞来源的外泌体(mesenchymal stem cell-derived exosome,MSC-Exo)通过降低Smad2/3磷酸化水平,抑制高糖诱导的α-SMA表达。综上所述,高糖通过激活TGF-β1信号通路导致BJ细胞的转分化,而MSC-Exo通过抑制该通路防止BJ细胞的转分化。
引用
收藏
页码:916 / 925
页数:10
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