MicroRNA-126/stromal cell-derived factor 1/C-X-C chemokine receptor type 7 signaling pathway promotes post-stroke angiogenesis of endothelial progenitor cell transplantation

Shan,Caiyun; Ma,Yongsheng

doi:10.3892/mmr.2018.8513

MicroRNA-126/stromal cell-derived factor 1/C-X-C chemokine receptor type 7 signaling pathway promotes post-stroke angiogenesis of endothelial progenitor cell transplantation

Authors:
- Caiyun Shan
- Yongsheng Ma
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Affiliations: Department of Geriatrics, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
Published online on: January 29, 2018 https://doi.org/10.3892/mmr.2018.8513
Pages: 5300-5305

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Abstract

Stroke is the most common cause of mortality worldwide. Post-stroke angiogenesis is of great significance to the treatment of strokes. The aim of the present study was to investigate the mechanism underlying the angiogenesis-promoting effect of microRNA‑126 (miR‑126)‑associated signaling pathways using a stroke model in vivo and a cell migration model in vitro. Bone marrow‑derived endothelial progenitor cells (EPCs) were extracted and identified using a density gradient method. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to examine the expression levels of miR‑126 and C‑X‑C chemokine receptor type 7 (CXCR7). Target genes of miR‑126 were analyzed using TargetScan software version 7.1 (www.targetscan.org/). In addition, a reporter gene assay and RT‑qPCR were performed to determine the target genes of miR‑126. The effect of miR‑126 on cell migration was examined using a cell migration model in vitro and a middle cerebral artery occlusion model of mice was established in vivo. The miR‑126 antagomir‑treated EPCs were infused into stroke mice. Microvessel density, nerve function score and infarction volume were assessed. Flow cytometric analysis indicated that cluster of differentiation (CD)34, CD133 and vascular endothelial growth factor receptor 2 were partly expressed on the cell surface of bone marrow‑derived EPCs. In addition, the expression levels of Di‑acetylated‑low density lipoprotein and Ulex europaeus agglutinin 1 were positive. Stromal cell‑derived factor 1 (SDF-1) was identified as a target gene of miR‑126, which was confirmed by a reporter gene assay and RT‑qPCR. Cell migration examination demonstrated that the neutralizing antibody of CXCR7 blocked miR‑126 angomir‑induced migration of EPCs. Microvessel density increased, while nerve function score and infarction volume decreased following infusion of miR-126 angomir‑treated EPCs. Furthermore, miR‑126 angomir improved the efficacy of EPC treatment. Thus, miR‑126 improved the migration of EPCs via the miR‑126/SDF‑1/CXCR7 signaling pathway.

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