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Dimethyloxalyl Glycine Regulates the HIF-1 Signaling Pathway in Mesenchymal Stem Cells

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Abstract

Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewal and multidirectional differentiation capabilities. Dimethyloxalyl glycine (DMOG) mobilizes MSCs, and the hypoxia inducible factor-1 (HIF-1) signaling pathway plays an important role in MSC mobilization. We aimed to investigate the effect of DMOG on the HIF-1 pathway in MSCs. Rats were treated with DMOG, and the numbers of peripheral blood MSCs (PB-MSCs) and bone marrow MSCs (BM-MSCs) were detected by the Colony-forming unit fibroblastic (CFU-F) method. The growth curve, cell cycle and migration ability of PB-MSCs and BM-MSCs were detected by CCK-8, Flow cytometry and Transwell assays. Western blotting and real-time qPCR were used to detect the expression of the HIF-1 pathway. The number of bone marrow microvessels was detected by immunohistochemistry. DMOG significantly increased the numbers of PB-MSCs and BM-MSCs (P < 0.05). Further, the MSCs in peripheral blood and bone marrow still had the ability to proliferate and migrate after mobilization by DMOG. The expression levels of HIF-1α, stromal cell-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) in MSCs were significantly regulated by DMOG (P < 0.05). The number of bone marrow microvessels decreased after the VEGF/VEGFR signaling pathway was blocked by SU5416 (P < 0.05). Therefore, these findings demonstrated that DMOG regulates the HIF-1α signaling pathway and promotes biological effects in MSCs.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Grant No. 31570994) and Natural Science Foundation of Zhejiang Province, China (Grant No. LY15C100001).

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  1. Binjie Zhou and Tingting Ge contributed equally to this work.

Authors and Affiliations

  1. College of Life Science, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, Zhejiang, 310053, People’s Republic of China

    Binjie Zhou, Tingting Ge, Liping Zhou, Lixia Jiang, Lujie Zhu, Panpan Yao & Qin Yu

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  1. Binjie Zhou
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Zhou, B., Ge, T., Zhou, L. et al. Dimethyloxalyl Glycine Regulates the HIF-1 Signaling Pathway in Mesenchymal Stem Cells. Stem Cell Rev and Rep 16, 702–710 (2020). https://doi.org/10.1007/s12015-019-09947-7

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