Pro‑angiogenic microRNA‑296 upregulates vascular endothelial growth factor and downregulates Notch1 following cerebral ischemic injury.
The present study examined the association between microRNA (miR)‑296 and angiogenesis following cerebral ischemic injury, and the underlying mechanisms. A cerebral ischemic model was established in rats via right middle cerebral artery occlusion. The animals were randomly divided into four groups (baseline, 1 day, 3 day and 7 day). Quantitative polymerase chain reaction and western blot analyses were performed to examine the expression levels of miR‑296 and hepatocyte growth factor‑regulated tyrosine kinase substrate (HGS), respectively. Angiogenesis was assessed by examining microvessel density. The results demonstrated that miR‑296 and angiogenesis were significantly upregulated, while HGS was significantly downregulated following ischemic injury. Adenovirus‑mediated overexpression of miR‑296 markedly enhanced the formation of capillary‑like structures in human umbilical vein endothelial cells, parallel with significantly increased expression levels of vascular endothelial growth factor (VEGF) and VEGF receptor 2, and reduced expression levels of DLL4 and Notch1. The results of the present study provided in vivo and in vitro evidence suggesting that miR‑296 promotes angiogenesis in the ischemic brain through upregulating VEGF and downregulating Notch1 following cerebral ischemic injury.
Institute of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Jie
J
Feng
Institute of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Tianxiang
T
Huang
Institute of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Qing
Q
Huang
Institute of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Hua
H
Chen
Institute of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Yu
Y
Li
Institute of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Wei
W
He
Institute of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Gui-Bin
GB
Wang
Institute of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Le
L
Zhang
Institute of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Jian
J
Xia
Institute of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Ning
N
Zhang
Institute of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Yunhai
Y
Liu
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism; D002536:Cerebral Arteries / Q000378:metabolism; D015536:Down-Regulation; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009389:Neovascularization, Pathologic; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D056827:Endosomal Sorting Complexes Required for Transport; C000610757:MIRN296 microRNA, rat; D035683:MicroRNAs; C497763:Notch1 protein, rat; D010750:Phosphoproteins; D051881:Receptor, Notch1; D042461:Vascular Endothelial Growth Factor A; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate