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Title

MiR-205 is downregulated in hereditary hemorrhagic telangiectasia and impairs TGF-beta signaling pathways in endothelial cells

AuthorsTabruyn, Sebastien P.; Hansen, Sylvain; Ojeda-Fernández, María Luisa ; Bovy, Nicolas; Zarrabeitia, Roberto; Recio-Poveda, Lucía; Bernabéu, Carmelo ; Martial, Joseph A.; Botella, Luisa María ; Struman, Ingrid
KeywordsHereditary hemorrhagic telangiectasia
MicroRNA
TGF-beta
Issue Date26-Jun-2013
PublisherSpringer
CitationAngiogenesis 16 (4) 877-887 (2013)
AbstractHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by arteriovenous malformations and hemorrhages. This vascular disease results mainly from mutations in 2 genes involved in the TGF-β pathway (ENG and ALK1) that are exclusively expressed by endothelial cells. The present study identified miR-27a and miR-205 as two circulating miRNAs differentially expressed in HHT patients. The plasma levels of miR-27a are elevated while those of miR-205 are reduced in both HHT1 and HHT2 patients compared to healthy controls. The role of miR-205 in endothelial cells was further investigated. Our data indicates that miR-205 expression displaces the TGF-β balance towards the anti-angiogenic side by targeting Smad1 and Smad4. In line, overexpression of miR-205 in endothelial cells reduces proliferation, migration and tube formation while its inhibition shows opposite effects. This study not only suggests that detection of circulating miRNA (miR-27a and miR-205) could help for the screening of HHT patients but also provides a functional link between the deregulated expression of miR-205 and the HHT phenotype. © 2013 Springer Science+Business Media Dordrecht.
Description20 p.-6 fig.
Publisher version (URL)http://dx.doi.org/10.1007/s10456-013-9362-9
URIhttp://hdl.handle.net/10261/100430
DOI10.1007/s10456-013-9362-9
ISSN0969-6970
E-ISSN1573-7209
Appears in Collections:(CIB) Artículos
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