Abstract
Hereditary 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Division / drug effects
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Cell Movement / drug effects
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Cells, Cultured
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Down-Regulation
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Endothelial Cells / metabolism*
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Gene Expression Regulation / physiology
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Gene Knockdown Techniques
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Human Umbilical Vein Endothelial Cells
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Humans
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / biosynthesis
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MicroRNAs / blood
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MicroRNAs / genetics
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MicroRNAs / physiology*
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Neovascularization, Pathologic / blood
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Neovascularization, Pathologic / genetics*
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Neovascularization, Pathologic / physiopathology
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Oligonucleotides, Antisense / pharmacology
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Phenotype
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ROC Curve
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Receptors, Transforming Growth Factor beta / physiology
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Signal Transduction / genetics
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Signal Transduction / physiology*
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Smad1 Protein / biosynthesis
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Smad1 Protein / genetics
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Smad4 Protein / biosynthesis
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Smad4 Protein / genetics
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Telangiectasia, Hereditary Hemorrhagic / blood
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Telangiectasia, Hereditary Hemorrhagic / diagnosis
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Telangiectasia, Hereditary Hemorrhagic / genetics*
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Telangiectasia, Hereditary Hemorrhagic / physiopathology
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Transcriptome*
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Transforming Growth Factor beta / pharmacology
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Transforming Growth Factor beta / physiology*
Substances
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MIRN205 microRNA, human
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MIRN27 microRNA, human
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MicroRNAs
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Oligonucleotides, Antisense
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Receptors, Transforming Growth Factor beta
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SMAD1 protein, human
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SMAD4 protein, human
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Smad1 Protein
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Smad4 Protein
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Transforming Growth Factor beta