MicroRNA-210 Promotes Accumulation of Neural Precursor Cells Around Ischemic Foci After Cerebral Ischemia by Regulating the SOCS1-STAT3-VEGF-C Pathway.

BACKGROUND: Neural precursor cell (NPC) migration toward lesions is key for neurological functional recovery. The neovasculature plays an important role in guiding NPC migration. MicroRNA-210 (miR-210) promotes angiogenesis and neurogenesis in the subventricular zone and hippocampus after cerebral ischemia; however, whether miR-210 regulates NPC migration and the underlying mechanism is still unclear. This study investigated the role of miR-210 in NPC migration. METHODS AND RESULTS: Neovascularization and NPC accumulation was detected around ischemic foci in a mouse model of middle cerebral artery occlusion (MCAO) and reperfusion. Bone marrow-derived endothelial progenitor cells (EPCs) were found to participate in neovascularization. miR-210 was markedly upregulated after focal cerebral ischemia/reperfusion. Overexpressed miR-210 enhanced neovascularization and NPC accumulation around the ischemic lesion and vice versa, strongly suggesting that miR-210 might be involved in neovascularization and NPC accumulation after focal cerebral ischemia/reperfusion. In vitro experiments were conducted to explore the underlying mechanism. The transwell assay showed that EPCs facilitated NPC migration, which was further promoted by miR-210 overexpression in EPCs. In addition, miR-210 facilitated VEGF-C (vascular endothelial growth factor C) expression both in vitro and in vivo. Moreover, the luciferase reporter assay demonstrated that miR-210 directly targeted the 3' untranslated region of SOCS1 (suppressor of cytokine signaling 1), and miR-210 overexpression in HEK293 cells or EPCs decreased SOCS1 and increased STAT3 (signal transducer and activator of transcription 3) and VEGF-C expression. When EPCs were simultaneously transfected with miR-210 mimics and SOCS1, the expression of STAT3 and VEGF-C was reversed. CONCLUSIONS: miR-210 promoted neovascularization and NPC migration via the SOCS1-STAT3-VEGF-C pathway.