MiR-۱۰۳ regulates the angiogenesis of ischemic stroke rats by targeting vascular endothelial growth factor (VEGF)

Objective(s): To investigate the effect of miR-۱۰۳ on the angiogenesis of ischemic stroke rats via targeting vascular endothelial growth factor (VEGF) at the molecular level. Materials and Methods: Rat models had received the middle cerebral artery occlusion (MCAO) or sham operation before grouping, and cell models of oxygen-glucose deprivation (OGD) were performed. FITC-dextran, matrigel, and Trans-well assays were used to evaluate the vascular density, tube formation, and cell migration respectively. The expression levels of miR-۱۰۳ and VEGF were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Dual-luciferase assay was used for analyzing the targeting relationship between miR-۱۰۳ and VEGF. Results: We found the reduced miR-۱۰۳ in rats after MCAO. Down-regulating miR-۱۰۳ with the miR-۱۰۳ inhibitor enhanced VEGF, ameliorated the neurological scores, decreased infarct volume, and increased vascular density in rats after MCAO. Besides, in OGD human umbilical vein endothelial cells (HUVECs), inhibition of miR-۱۰۳ could promote the increase of tube length and the migration of cells. Additionally, we found that miR-۱۰۳ could directly target VEGF and thereby lead to the down-expression of VEGF. Meanwhile, si-VEGF could reverse the effect of miR-۱۰۳ inhibitor on angiogenesis in rats subjected to MCAO. Conclusion: Inhibition of miR-۱۰۳ could promote ischemic stroke angiogenesis and reduce infarction volume via enhancing VEGF, which provides a new target for the clinical treatment of ischemic stroke.

Keywords:

Infarction , Ischemia , Middle cerebral artery , MIRN۱۰۳ microRNA , Stroke , Vascular endothelial-growth factor A