ReferenceID 142

miR-370 inhibits the angiogenic activity of endothelial cells by targeting smoothened (SMO) and bone morphogenetic protein (BMP)-2

FASEB J

MicroRNAs (miRNAs) crucially modulate fundamental biologic processes such as angiogenesis. In the present study, we focused on the molecular function of miRNA-370-3p (miR-370) in regulating the angiogenic activity of end

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Reference Id
142
Evidence Id
16732
Core Evidence Id
16732
Source Reference Id
246
Herb2 Reference Id
HBREF000459
Subject Paper Key
HBIN022330_30865837
Pubmed Id
30865837
Doi
10.1096/fj.201802085RR
Paper Title
miR-370 inhibits the angiogenic activity of endothelial cells by targeting smoothened (SMO) and bone morphogenetic protein (BMP)-2
Paper Abstract
MicroRNAs (miRNAs) crucially modulate fundamental biologic processes such as angiogenesis. In the present study, we focused on the molecular function of miRNA-370-3p (miR-370) in regulating the angiogenic activity of endothelial cells (ECs). Transfection with miR-370 mimic (miR-370m) significantly inhibited the sprouting of human dermal microvascular EC (HDMEC) and HUVEC spheroids and mouse aortic rings, whereas miR-370 inhibitor (miR-370i) promoted sprout formation. Additional in vitro assays demonstrated the pleiotropic inhibitory effects of miR-370m on HDMEC proliferation, migration, and tube formation. Moreover, Matrigel plugs containing miR-370m-transfected HDMECs exhibited a reduced microvessel density after implantation into CD1 nude mice when compared with controls. In contrast, miR-370i exerted proangiogenic effects. Mechanistic analyses revealed that miR-370 directly targets smoothened (SMO) and down-regulates bone morphogenetic protein (BMP)-2 expression in HDMECs. Accordingly, inhibition of SMO by cyclopamine reversed miR-370i-induced HDMEC proliferation and migration. In addition, BMP-2 treatment counteracted miR-370m-suppressed tube formation of HDMECs, whereas blockade of BMP-2 with neutralizing antibody significantly inhibited miR-370i-induced tube formation. Taken together, these novel findings indicate that miR-370 is a potent inhibitor of angiogenesis, which directly targets SMO and BMP-2.-Gu, Y., Becker, V., Zhao, Y., Menger, M. D., Laschke, M. W. miR-370 inhibits the angiogenic activity of endothelial cells by targeting smoothened (SMO) and bone morphogenetic protein (BMP)-2.
Journal
FASEB J
Publish Year
2019
Experiment Subject
cd1 nude mice,human dermal microvascular ec,huvec spheroids , mouse aortic rings
Experiment Type
Animal & Cell Experiment
Phenotype Related
Paper Title Cn
Paper Title En
miR-370 inhibits the angiogenic activity of endothelial cells by targeting smoothened (SMO) and bone morphogenetic protein (BMP)-2
Bilingual Status
semi_complete