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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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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DOI: https://doi.org/10.1038/gt.2013.55
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