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Buyang Huanwu Decoction (BYHWD) Enhances Angiogenic Effect of Mesenchymal Stem Cell by Upregulating VEGF Expression After Focal Cerebral Ischemia

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Abstract

Buyang Huanwu decoction (BYHWD) has been used for centuries to treat paralysis and stroke. Previously, we have demonstrated that BYHWD combined with mesenchymal stem cell (MSC) transplantation attenuates ischemic injury partly by upregulating angiogenesis. However, the mechanisms of this drug for stroke treatment are not completely understood. Here, we aimed to clarify the mechanism of BYHWD on angiogenesis mediated by MSCs. Firstly, we verified microvessels with a size of 50–100 nm produced by either MSCs or MSCs treated by 500 μg/ml BYHWD. These exosomes were purified and found to be able to activate vascular endothelial growth factor (VEGF) expression in endothelial cells (ECs). Moreover, exosomes from MSCs and MSCs treated by BYHWD induced elevated microRNA (miRNA)-126 expression and reduced miR-221 and miR-222 expression. In MSCs, disruption of dicer, an enzyme responsible for miRNA maturation, by dicer small interfering RNA (siRNA), or RNase pretreatment abolished this ability of the exosomes. Additionally, exosomes from MSCs treated by BYHWD promoted VEGF and Ki-67 expression and augmented vascular density in rat brain after bilateral carotid artery ligation. In conclusion, our study revealed that BYHWD exposure augmented angiogenetic miRNA and VEGF expression in exosomes secreted by MSCs and elevated angiogenesis in rat brain.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (No. 81072799)

Conflict of Interest

No conflicts were declared.

Authors’ Contributions

Junhong Yang and Feng Gao contributed to conception and design and acquisition, analysis, and interpretation of data. Ying Liu has been involved in drafting the manuscript or revising it critically for important intellectual content. Yunke Zhang has given final approval of the version to be published. Di Zhang agreed to be accountable for all aspects of the work.

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    Authors and Affiliations

    1. The First Department of Encephalopathy, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, China

      Junhong Yang

    2. Department of Neuroimmunology, Henan Province Academy of Medical and Pharmaceutical, Zhengzhou University, Zhengzhou, 450052, China

      Feng Gao

    3. The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine, No. 6, Dongfeng Road, Jinshui District, Zhengzhou, 450002, China

      Yunke Zhang

    4. Department of Rehabilitation, Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou, 450007, China

      Ying Liu

    5. Luoyang Center Hospital, Luoyang, 471000, China

      Di Zhang

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    1. Junhong Yang
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    Correspondence to Yunke Zhang.

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    Junhong Yang and Feng Gao contributed equally to this work.

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    Yang, J., Gao, F., Zhang, Y. et al. Buyang Huanwu Decoction (BYHWD) Enhances Angiogenic Effect of Mesenchymal Stem Cell by Upregulating VEGF Expression After Focal Cerebral Ischemia. J Mol Neurosci 56, 898–906 (2015). https://doi.org/10.1007/s12031-015-0539-0

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    • DOI: https://doi.org/10.1007/s12031-015-0539-0

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