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.