miR-16 inhibits the proliferation and angiogenesis-regulating potential of mesenchymal stem cells in severe pre-eclampsia

Authors

  • Yaping Wang,

    1. Immunology and Reproductive Biology Laboratory, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China
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    • These authors contributed equally to this work.
  • Hongye Fan,

    1. Immunology and Reproductive Biology Laboratory, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China
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    • These authors contributed equally to this work.
  • Guangfeng Zhao,

    1. The Affiliated Drum Tower Hospital of Nanjing University Medical School, China
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  • Dan Liu,

    1. Immunology and Reproductive Biology Laboratory, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China
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  • Leilei Du,

    1. Immunology and Reproductive Biology Laboratory, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China
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  • Zhiqun Wang,

    1. The Affiliated Drum Tower Hospital of Nanjing University Medical School, China
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  • Yali Hu,

    Corresponding author
    1. The Affiliated Drum Tower Hospital of Nanjing University Medical School, China
    • Immunology and Reproductive Biology Laboratory, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China
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  • Yayi Hou

    Corresponding author
    1. Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China
    • Immunology and Reproductive Biology Laboratory, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China
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Correspondence

Y. Hou, Immunology and Reproduction Biology Lab Medical School, Nanjing University, Nanjing 210093, China

Fax: +86 25 83686441

Tel: +86 25 83686441

E-mail: yayihou@nju.edu.cn

Y. Hu, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China

Tel: +86 25 83321980

E-mail: yali_hu@hotmail.com

Abstract

Pre-eclampsia is thought to be a systemic disease of maternal endothelial cell dysfunctions. miRNAs regulate various basic biological functions in cells, including stem cells. Mesenchymal stem cells exist in almost all tissues and are the key cellular source for tissue repair and regeneration. Our aims are to investigate whether miRNAs regulate MSCs in fetal–maternal interfaces to influence the pathogenesis of pre-eclampsia. The differential expression of miRNAs in decidua-derived mesenchymal stem cells of all patients with severe pre-eclampsia (= 20) and normal groups (= 20) was first screened by microarray analysis and validated by quantitative real-time PCR analysis. The integrated bioinformatics analysis showed that miR-16 showed the highest number of connections in the miRNA GO network and the miRNA gene network. Moreover, over-expressed miR-16 inhibited the proliferation and migration of decidua-derived mesenchymal stem cells and induced cell-cycle arrest by targeting cyclin E1. Interestingly, over-expression of miR-16 by decidua-derived mesenchymal stem cells reduced the ability of human umbilical vein endothelial cells to form blood vessels and reduced the migration of trophoblast cells. Furthermore, decidua-derived mesenchymal stem cell-expressed endothelial growth factor VEGF-A was involved in migration of trophoblast cells and human umbilical vein endothelial cells as well as tube and network formation. Importantly, the levels of cyclin E1 and VEGF-A were negatively correlated with the level of miR-16 expression in decidua-derived mesenchymal stem cells from the patients with severe pre-eclampsia. Together, these data suggest that the alteration of miR-16 expression in decidua-derived mesenchymal stem cells may be involved in the development of pre-eclampsia.

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