Open AccessMicro RNA ‐210 Promotes Accumulation of Neural Precursor Cells Around Ischemic Foci After Cerebral Ischemia by Regulating the SOCS1–STAT3–VEGF‐C Pathway
Author(s) -
Meng ZhaoYou,
Kang HuaLi,
Duan Wei,
Zheng Jian,
Li QianNing,
Zhou ZhuJuan
Publication year - 2018
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.116.005052
Subject(s) - medicine , angiogenesis , neovascularization , ischemia , subventricular zone , stat3 , microrna , cancer research , vascular endothelial growth factor , neural stem cell , microbiology and biotechnology , pathology , signal transduction , biology , stem cell , biochemistry , gene , vegf receptors
Background Neural precursor cell ( NPC ) migration toward lesions is key for neurological functional recovery. The neovasculature plays an important role in guiding NPC migration. Micro RNA ‐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 ( EPC s) 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 EPC s facilitated NPC migration, which was further promoted by miR‐210 overexpression in EPC s. 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 HEK 293 cells or EPC s decreased SOCS 1 and increased STAT3 (signal transducer and activator of transcription 3) and VEGF‐C expression. When EPC s were simultaneously transfected with miR‐210 mimics and SOCS 1, the expression of STAT 3 and VEGF ‐C was reversed. Conclusions miR‐210 promoted neovascularization and NPC migration via the SOCS 1– STAT 3– VEGF ‐C pathway.