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ILK promotes survival and self-renewal of hypoxic MSCs via the activation of lncTCF7-Wnt pathway induced by IL-6/STAT3 signaling

Gene Therapy volume 26, pages 165–176 (2019)Cite this article

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Abstract

Mesenchymal stem cells (MSCs) have been applied in treating various diseases including myocardial infarction (MI) and achieved a bit of success; however, the decreased survival rate of MSCs after transplantation greatly limited the efficacy for cell therapy. How to improve the MSC survival rate in stem cell transplantation has undoubtedly become urgent and genetic engineering may be an ideal and feasible way. In this study, we explored the effects on MSCs survival and self-renewal by overexpression of integrin-linked kinase (ILK) in MSCs under hypoxic stimulation and aimed to reveal the molecular mechanisms from the point of paracrine function of MSCs. We first found that overexpression of ILK induced the expression and secretion of IL-6 increased significantly in MSCs under hypoxic stimulation, and the survival and self-renewal of MSCs exposed to hypoxia were enhanced after ILK overexpression. Then the activation of JAK2/STAT3 signaling was detected because of the increased IL-6, and an lncRNA, named lncTCF7, was upregulated remarkably, promoting the activation of Wnt pathway that was required for keeping cell viability and stemness of MSCs. Moreover, we further verified that inhibition of STAT3 signaling by WP1066 and silencing lncTCF7 expression eliminated the protective effects of ILK overexpression on cell survival and self-renewal of MSCs under hypoxic sitmulation. In conclusion, our results uncovered a novel function of ILK to promote MSC survival and self-renewal, suggesting more application potentials of MSC cell therapy on MI.

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Acknowledgements

This work was supported by The General Program of Guangxi Natural Science Foundation (No. 2017GXNSFAA198214).

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Authors and Affiliations

  1. Department of Cardiology, Nanjing Lishui People’s Hospital, Zhongda Hospital Lishui Branch, Southeast University, 211200, Nanning, P.R. China

    Qing Mao

  2. Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, 530007, Nanning, P.R. China

    Xiu-Lin Liang

  3. Department of Cardiology, The Guangxi Zhuang Autonomous Region Brain Hospital, 545005, Liuzhou, P.R. China

    Yu-Fu Wu

  4. Department of Cardiology, The Second Affiliated Hospital of Guangxi Medical University, 530007, Nanning, P.R. China

    Yi-Heng Pang, Xiao-Jun Zhao & Yong-Xiang Lu

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  1. Qing Mao
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Correspondence to Qing Mao.

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Mao, Q., Liang, XL., Wu, YF. et al. ILK promotes survival and self-renewal of hypoxic MSCs via the activation of lncTCF7-Wnt pathway induced by IL-6/STAT3 signaling. Gene Ther 26, 165–176 (2019). https://doi.org/10.1038/s41434-018-0055-2

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