中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (23): 4253-4258.doi: 10.3969/j.issn.1673-8225.2012.23.015

• 干细胞因子及调控因子 stem cell factors and regulatory factors • 上一篇    下一篇

转化生长因子β1促进骨髓间充质干细胞迁移与上调Snail表达有关

郑丽芳1,2,梅元武2,张小乔2,张 红2   

  1. 1武汉科技大学附属天佑医院神经内科,湖北省武汉市 430064;
    2华中科技大学同济医学院附属协和医院神经内科,湖北省武汉市 430022
  • 收稿日期:2011-11-19 修回日期:2012-02-03 出版日期:2012-06-03 发布日期:2013-11-06
  • 通讯作者: 梅元武,主任医师,博士生导师,华中科技大学同济医学院附属协和医院神经内科,湖北省武汉市 430022
  • 作者简介:郑丽芳☆,女,1971年生,湖北省武汉市人,博士,副主任医师,主要从事脑血管疾病的康复治疗。

Transforming growth factor beta 1 promotes the migration of mesenchymal stem cells via upregulation of Snail expression

Zheng Li-fang1, 2, Mei Yuan-wu2, Zhang Xiao-qiao2, Zhang Hong2   

  1. 1Department of Neurology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430064, Hubei Province, China;
    2Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
  • Received:2011-11-19 Revised:2012-02-03 Online:2012-06-03 Published:2013-11-06
  • Contact: Mei Yuan-wu, Chief physician, Doctoral supervisor, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China meiyuanwu@sohu.com
  • About author:Zheng Li-fang☆, Doctor, Associate chief physician, Department of Neurology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430064, Hubei Province, China; Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China zlf027@163.com

摘要:

背景:转化生长因子β1可促进骨髓间充质干细胞迁移及增殖,但机制尚不清楚。
目的:观察转化生长因子β1对体外培养的骨髓间充质干细胞侵袭力的影响,以及对Snail、基质金属蛋白酶2表达的调节作用。
方法:采用密度梯度离心结合贴壁法分离、培养大鼠骨髓间充质干细胞。用改良的Transwell小室检测0,0.5,1,2,5,10 μg/L的转化生长因子β1对细胞迁移的影响。用脂质体转染针对Snail基因的特异性小分子干扰RNA至骨髓间充质干细胞,观察转染前后Snail和基质金属蛋白酶2 的表达。
结果与结论:外源性转化生长因子β1对骨髓间充质干细胞迁移的促进作用具有剂量依赖性,在2 μg/L时达到最高。在此浓度下,Snail、基质金属蛋白酶2 mRNA表达明显增高。Snail基因沉默可以明显抑制转化生长因子β1对基质金属蛋白酶2表达的促进作用。提示转化生长因子β1可通过促进骨髓间充质干细胞基质金属蛋白酶2的表达提高其迁移能力,此作用与上调Snail表达有关。

关键词: 转化生长因子β1, 骨髓间充质干细胞, Snail, 基质金属蛋白酶2, 基因沉默

Abstract:

BACKGROUND: Transformation growth factor β1 (TGF-β1) can promote bone marrow mesenchymal stem cells (BMSCs) migration and proliferation, but the underlying mechanisms remain unclear.
OBJECTIVE: To observe the invasiveness of TGF-β1 on BMSCs cultured in vitro, and to investigate regulatory effect on Snail and matrix metalloproteinase 2 (MMP-2) expression.
METHODS: Rat BMSCs were isolated and cultured with density gradient centrifugalization and adherence method. The influence of different concentrations of TGF-β1 on the BMSC migration was detected using the modified Transwell chambers. Small interfering RNA for Snail gene was synthesized and transfected into BMSCs by liposomel before TGF-β1 was treated, and the expression of Snail and MMP-2 before and after transfection were measured by western blot assay.
RESULTS AND CONCLUSION: The exogenous TGF-β1 can induce a dose-dependent increase in cell migration, which peaked at 2 μg/L. The expression levels of Snail mRNA and MMP-2 mRNA were significantly increased after 2 μg/L TGF-β1 treatment. Snail gene can effectively inhibit the expression of MMP-2 promoted by TGF-β1. Experimental findings indicate that TGF-β1 could increase the MMP-2 expression and then promote the BMSCs migration through the upregulation of the Snail expression.

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