Affiliation:
1. Department of Acupuncture and Rehabilitation, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing
210029, Jiangsu Province, China
Abstract
Background:
Acupuncture has been wildly applied for cerebral ischemia treatment in
China for thousands of years, while the specific mechanism remains uncertain. Recently, many studies
have shown that acupuncture promotes angiogenesis after ischemia occurs. Here, we examined
the effect of electro-acupuncture (EA) exosomes on angiogenesis in hypoxia-induced human umbilical
vein endothelial cells (HUVECs).
Objective:
To investigate whether EA exosomal miR-210 promotes angiogenesis in the hypoxiainduced
HUVECs via the HIF-1α/VEGF/Notch 1 signal pathway.
Methods:
The middle cerebral artery occlusion (MCAO) model was established and treated with EA
therapy. Then, exosomes were identified and isolated from rats' plasma in the MCAO+EA group by
transmission electron microscopy (TEM), surface markers expressions, and PKH26 reagent. MiR-
210 mimic, miR-210 inhibitor, and HIF-1α were transfected. Flow cytometry, CCK-8 assay, and
Transwell assay were conducted to assess the migration, apoptosis, and proliferation of each group
of cells. Western blot and quantitative PCR were performed to detect the CD34, HIF-1α, VEGF,
Notch 1, and miR-210 expression levels in each group.
Results:
MiR-210 was significantly upregulated in exosomes of the MCAO plasma, and further
enhanced by EA therapy. EA-EXOs and miR-210 mimic inhibited cell apoptosis, promoted cell
proliferation and cell migration in hypoxia-induced HUVECs. However, the miR-210 inhibitor reversed
the proliferation and migration number induced by EA-EXOs. Besides, EA-EXOs and miR-
210 mimic further enhanced those HIF-1α, VEGF, and Notch 1 levels compared to the hypoxia
treatment only. Silencing HIF-1α or miR-210 reversed the high expressions of those three angiogenic
factors induced by hypoxia and EA-EXO. qPCR showed similar trends with their relative
mRNAs. To analyze these associations quantificationally, Spearman's rank correlation coefficient
was calculated. As revealed by results, the expression of proteins and mRNA were highly correlative
with each other.
Conclusions:
These results indicated that EA-EXO miR-210 promotes angiogenesis in hypoxia conditions
via HIF-1α/VEGF/Notch 1 signal pathway.
Funder
National Natural Science Foundation of China
Peak Academic Talents of Jiangsu Hospital of Traditional Chinese Medicine
Publisher
Bentham Science Publishers Ltd.
Subject
Cellular and Molecular Neuroscience,Developmental Neuroscience,Neurology
Cited by
2 articles.
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