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MicroRNA-210 overexpression induces angiogenesis and neurogenesis in the normal adult mouse brain

Abstract

Angiogenesis and neurogenesis are crucial processes for brain tissue repair and remodeling after brain injury. Current study shows that microRNA-210 (miR-210) promotes vascular endothelial cell migration and tube formation under hypoxia in vitro. Whether miR-210 overexpression promotes focal angiogenesis and neurogenesis in the normal adult brain is unknown. Adult male C57BL/6 mice (n=54) underwent stereotactic injection of a lentiviral vector carrying miR-210 (LV-miR-210). Following 28 days of miR-210 gene transfer, endothelial cell and neural precursor cell proliferation, microvessel density and downstream angiogenic factor were genotyped. miR-210 was highly expressed in neurons, astrocytes and endothelial cells of the LV-miR-210-injected brain hemisphere. The endothelial cell proliferation and the number of newly formed microvessels were greatly increased in the LV-miR-210-treated mice compared with the controls (P<0.05). Neural progenitor cells in the subventricular zone were greatly increased compared with the controls (P<0.05). The data indicate that miR-210 is a key factor at the microRNA level in promoting angiogenesis and neurogenesis, which was associated with local increased vascular endothelial growth factor (VEGF) levels, suggesting that miR-210 may be a potential target for ischemic stroke therapy.

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Acknowledgements

This study is supported by 973 Program of NBRP, China (2011CB504405, GYY, YW), NSFC (30973097, GYY, 81200943, LZ), the Shanghai medical association (SHNR-003, LZ), Shanghai healthy bureau (20124217, LZ) and by the Science and Technology Commission of Shanghai Municipality (12ZR1418600, FY).

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Correspondence to Y Fu or G-Y Yang.

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Zeng, L., He, X., Wang, Y. et al. MicroRNA-210 overexpression induces angiogenesis and neurogenesis in the normal adult mouse brain. Gene Ther 21, 37–43 (2014). https://doi.org/10.1038/gt.2013.55

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