miR-376b-5p regulates angiogenesis in cerebral ischemia.
The profile of microRNAs (miRNAs) altered following middle cerebral artery occlusion (MCAO) and miRNAs are involved in angiogenesis following cerebral ischemia. miR‑376b‑5p was decreased following MCAO, however, whether miR‑376b‑5p is important in angiogenesis remains to be elucidated. The present study was designed to identify whether miR‑376b‑5p is involved in angiogenesis following cerebral ischemia and to elucidate the underlying mechanisms. A rat MCAO model was established and quantitative polymerase chain reaction was performed to analyze the mRNA expression level of miR‑376b‑5p for 1 to 7 days. In addition, the density of microvessels and the relative mRNA and protein levels of hypoxia‑inducible factor‑1 α (HIF‑1α), vascular endothelial growth factor A (VEGFA) and Notch1 were measured. The miR‑376b‑5p mimic or the miR‑376b‑5p inhibitor were transfected into hypoxic human umbilical vein endothelial cells (HUVECs), and the proliferation, migration and tube formation were measured. To further examine the underlying mechanisms, shRNA was transfected into cells to knock down HIF‑1α, and angiogenesis and the expression of associated molecules, including HIF‑1α, VEGFA and Notch1 were compared between each group. Our results demonstrated that miR‑376b‑5p repressed angiogenesis in vivo and in vitro, and miR‑376b‑5p inhibited angiogenesis in HUVECs by targeting the HIF‑1α‑mediated VEGFA/Notch1 signaling pathway. These findings provide new insights into angiogenesis therapy for cerebral ischemia.
Department of Neurology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Ling-Juan
LJ
Li
Department of Neurology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Qing
Q
Huang
Department of Neurology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Ning
N
Zhang
Department of Neurology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Gui-Bin
GB
Wang
Department of Neurology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Yun-Hai
YH
Liu
D000818:Animals; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D015536:Down-Regulation; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C573498:MIRN376C microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor