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|Title:||miR-370 inhibits the angiogenic activity of endothelial cells by targeting smoothened (SMO) and bone morphogenetic protein (BMP)-2|
Menger, Michael D.
Laschke, Matthias W.
|Year of Publication:||2019|
|Free key words:||miRNA|
|DDC notations:||610 Medicine and health|
|Publikation type:||Journal Article|
|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. FASEB J. 33, 7213–7224 (2019). www.fasebj.org|
|DOI of the first publication:||10.1096/fj.201802085RR|
|URL of the first publication:||https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201802085RR|
|Link to this record:||urn:nbn:de:bsz:291--ds-393906|
|Date of registration:||28-Mar-2023|
|Description of the related object:||Supporting Information|
|Faculty:||M - Medizinische Fakultät|
|Department:||M - Chirurgie|
|Professorship:||M - Prof. Dr. Michael D. Menger|
|Collections:||SciDok - Der Wissenschaftsserver der Universität des Saarlandes|
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