S1PR1/3介导骨髓间充质干细胞向肌成纤维细胞分化的信号通路探讨

doi:10.3969/j.issn.1006-7795.2017.02.022

首都医科大学学报 ›› 2017, Vol. 38 ›› Issue (2): 277-281.doi: 10.3969/j.issn.1006-7795.2017.02.022

S1PR1/3介导骨髓间充质干细胞向肌成纤维细胞分化的信号通路探讨

杨苑儒¹, 周璇¹, 张若辰¹, 李丽英², 杨乐²

1. 首都医科大学2013级医学实验技术专业, 北京 100069;
2. 首都医科大学基础医学院细胞生物学系, 北京 100069

收稿日期:2016-06-02 出版日期:2017-03-21 发布日期:2017-04-17
通讯作者: 杨乐,E-mail:yangle@ccmu.edu.cn E-mail:yangle@ccmu.edu.cn
基金资助:
北京市自然科学基金（7164237），北京市优秀人才培养资助（2014000020124G156）

Signaling of bone marrow mesenchymal stem cell differentiation to myofibroblasts mediated by S1PR1/3

Yang Yuanru¹, Zhou Xuan¹, Zhang Ruochen¹, Li Liying², Yang Le²

1. Grade 2013 Medical Laboratory Animal Science, Capital Medical University, Beijing 100069;
2. Department of Cell Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

Received:2016-06-02 Online:2017-03-21 Published:2017-04-17
Supported by:
This study was supported by Natural Science Foundation of Beijing (7164237), Beijing Municipal Foundation for the Excellent Talents (2014000020124G156)

摘要/Abstract

摘要： 目的在转化生长因子β1（transforming growth factor β1，TGFβ1）诱导的分化模型中探讨RhoA信号对于磷酸鞘氨醇受体1/3（sphingosine 1-phosphate receptor 1/3，S1PR1/3）介导骨髓间充质干细胞（bone marrow mesenchymal stem cell，BMSC）向肌成纤维细胞（myofibroblast，MF）分化的影响及其机制。方法分离并培养小鼠原代BMSC，TGFβ1诱导其分化。采用qRT-PCR检测分化标志物平滑肌肌动蛋白α（α-smooth muscle actin，αSMA）、Ⅰ型胶原[procollagen α1（Ⅰ），Col α1（Ⅰ）]和Ⅲ型胶原[Col α1（Ⅲ）]的mRNA表达;采用Pull-down试剂盒检测RhoA的活化。结果 TGFβ1能够显著上调BMSC细胞中分化标志物αSMA、Col α1（Ⅰ）和Col α1（Ⅲ）的mRNA表达，呈现剂量依赖效应。TGFβ1能够激活小G蛋白RhoA，该作用可以被S1PR1或S1PR3拮抗剂所阻断。RhoA抑制剂C3转移酶能够阻断TGFβ1诱导的αSMA、Col α1（Ⅰ）和Col α1（Ⅲ）mRNA水平的上调。结论 RhoA信号参与了S1PR1/3介导的BMSC向MF的分化。

关键词: 小鼠, 骨髓间充质干细胞, 磷酸鞘氨醇受体, RhoA

Abstract: Objective Aim of this study is to explore the role of RhoA in transforming growth factor β1 (TGFβ1)-induced bone marrow mesenchymal stem cell (BMSC) differentiation to myofibroblast (MF) mediated by sphingosine 1-phosphate receptor 1/3 (S1PR1/3). Methods Serum-starved primary cultured mouse BMSCs were stimulated by a series dose of TGFβ1. Expression of α-smooth muscle actin (αSMA), procollagen α1(Ⅰ)[Col α1(Ⅰ)] and procollagen α1(Ⅲ)[Col α1(Ⅲ)] was measured by qRT-PCR. Activated RhoA induced by TGFβ1 in BMSCs was determined by Pull-down assay. Results TGFβ1 induced an up-regulation of αSMA, Col α1(Ⅰ) and Col α1(Ⅲ) mRNA levels in BMSCs. TGFβ1 triggered the activation of RhoA, which can be blocked by S1PR1/3 antagonists. RhoA inhibitor C3 Transferase reversed the up-regulation of αSMA, Col α1(Ⅰ) and Col α1(Ⅲ) mRNA expression induced by TGFβ1. Conclusion RhoA is involved in the differentiation of BMSC to MF induced by TGFβ1.

Key words: mouse, bone marrow mesenchymal stem cell, sphingosine 1-phosphate receptor, RhoA

中图分类号:

杨苑儒, 周璇, 张若辰, 李丽英, 杨乐. S1PR1/3介导骨髓间充质干细胞向肌成纤维细胞分化的信号通路探讨[J]. 首都医科大学学报, 2017, 38(2): 277-281.

Yang Yuanru, Zhou Xuan, Zhang Ruochen, Li Liying, Yang Le. Signaling of bone marrow mesenchymal stem cell differentiation to myofibroblasts mediated by S1PR1/3[J]. Journal of Capital Medical University, 2017, 38(2): 277-281.

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S1PR1/3介导骨髓间充质干细胞向肌成纤维细胞分化的信号通路探讨

Signaling of bone marrow mesenchymal stem cell differentiation to myofibroblasts mediated by S1PR1/3

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