TGF-β1/Smad 信号通路的激活 对招募间充质干细胞在血管损伤中的表达变化及意义

魏翠蕾 , , 邹泓 , 段军仓 , 刘克坚 , 赵 伟 , 王成燕 , 蒋金芳 , 梁伟华 , 王毅训 , 庞丽娟 , 李 锋

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石河子大学学报 ›› 2014, Vol. 32 ›› Issue (6) : 720-726.
医学·药学

TGF-β1/Smad 信号通路的激活 对招募间充质干细胞在血管损伤中的表达变化及意义

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Activation of TGF-β1/Smad Signaling Recruited of MSCs in Balloon Injured Artery and its Significance

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摘要

探讨转化生长因子 -β1(Transforming growth factor,TGF-β1)在介入性血管损伤后新生内膜的形成过程中发 挥的作用以及 TGF-β1 对间充质干细胞(MSCs)可能与新生内膜的发生发展存在的关系。本实验通过建立大鼠颈总 动脉球囊损伤模型,检测动脉损伤后不同时间点新生内膜中各蛋白的表达变化,以探讨 TGF-β1/Smad 信号通路的 活化与内膜增生以及 TGF-β1 与 MSCs 招募的关系。以计算机图像分析系统计算损伤血管内膜增生程度的变化,免 疫 组 化 EnVision 二 步 法 检 测 血 管 损 伤 后 7、14、21 d 时 新 生 内 膜 中 TGF-β1、P-Smad2/3、Nestin 及 Ki-67 的 蛋 白 表 达。结果显示:(1)大鼠颈动脉球囊损伤后不同时间点血管内膜增生程度不同,损伤后 7 d 开始形成少量内膜,14 d 显著增多,21 d 达最大厚度;(2)TGF-β1、 P-Smad2/3 于新生内膜中的表达含量变化与 Ki-67 阳性指数正相关; (3)Nestin 在损伤血管内的表达阳性指数与 TGF-β1 的表达量正相关。由此可知,TGF-β1 对血管损伤后内膜增生 的促进作用可能通过 Smad 经典信号通路,且在损伤过程中,TGF-β1 的分泌可能招募循环中的 MSCs 至损伤血管 处,共同参与损伤后的血管重塑。

Abstract

Mechanisms of Transforming growth factor (TGF)-β1 involving in neointima formation are still controversial.It has been suggested that the recruited mesenchymal stem cells (MSCs) following arterial injury could contribute to neointima formation,but the role of downstream signaling and the contribution of the recruited MSCs are still unknown.In this study,we observed the correlations between expression and distribution of TGF-β1/Smad signaling pathway proteins and recruitment of MSC cells in the process of neointima formation using a rat model for balloon-induced carotid artery injury.It was found that the neointimathickness increased to the maximum at 21 days; Ki-67 expression was increased consistent with the elevation of TGF-β1 and p-Smad2/3 levels; MSCs accumulated at the lumen side of neointima.Herein,It was demonstrate that TGF-β1induced the proliferation of neointima cells by Smad signaling and MSCs recruited by TGF-β1/Smad signaling was possibly involved in the proliferation of neointima via modulation of TGF-β1/Smads signaling

关键词

球囊损伤 / 再狭窄 / 转化生长因子 -β1 / 间充质干细胞

Key words

TGF-β1/Smad signaling pathway / MSCs / balloon injury / restenosis

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魏翠蕾 , , 邹泓 , 段军仓 , 刘克坚 , 赵 伟 , 王成燕 , 蒋金芳 , 梁伟华 , 王毅训 , 庞丽娟 , 李 锋 . TGF-β1/Smad 信号通路的激活 对招募间充质干细胞在血管损伤中的表达变化及意义. 石河子大学学报. 2014, 32(6): 720-726
WEI Cuilei , ZOU Hong , DUAN Juncang , LIU Kejian , ZHAO Wei , WANG Chengyan , JIANG Jinfang , LIANG Weihua , WANG Yixun , PANG Lijuan , LI Feng. Activation of TGF-β1/Smad Signaling Recruited of MSCs in Balloon Injured Artery and its Significance. Journal of Shihezi University. 2014, 32(6): 720-726

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基金

国家自然科学基金项目(81160018),新疆兵团博士资金专项(2014BB018),石河子大学杰出青年培育计划(2013ZRKXJQ05)
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