The miR-126 regulates Angiopoietin-1 signaling and vessel maturation by targeting p85β

Roberto Sessa, Giorgio Seano, Laura di Blasio, Paolo Armando Gagliardi, Claudio Isella, Enzo Medico, Franco Cotelli, Federico Bussolino, Luca Primo

Research output: Contribution to journalArticle

Abstract

Blood vessel formation depends on the highly coordinated actions of a variety of angiogenic regulators. Vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1) are both potent and essential proangiogenic factors with complementary roles in vascular development and function. Whereas VEGF is required for the formation of the initial vascular plexus, Ang-1 contributes to the stabilization and maturation of growing blood vessels.Here, we provide evidence of a novel microRNA (miRNA)-dependent molecular mechanism of Ang-1 signalling modulation aimed at stabilizing adult vasculature. MiRNAs are short non-coding RNA molecules that post-trascriptionally regulate gene expression by translational suppression or in some instances by cleavage of the respective mRNA target. Our data indicate that endothelial cells of mature vessels express high levels of miR-126, which primarily targets phosphoinositide-3-kinase regulatory subunit 2 (p85β). Down-regulation of miR-126 and over-expression of p85β in endothelial cells inhibit the biological functions of Ang-1. Additionally, knockdown of miR-126 in zebrafish resulted in vascular remodelling and maturation defects, reminiscent of the Ang-1 loss-of-function phenotype. Our findings suggest that miR-126-mediated phosphoinositide-3-kinase regulation, not only fine-tunes VEGF-signaling, but it strongly enhances the activities of Ang-1 on vessel stabilization and maturation.

Original languageEnglish
Pages (from-to)1925-1935
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1823
Issue number10
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Angiopoietin-1
Blood Vessels
Vascular Endothelial Growth Factor A
Class Ia Phosphatidylinositol 3-Kinase
Endothelial Cells
Untranslated RNA
1-Phosphatidylinositol 4-Kinase
MicroRNAs
Down-Regulation
Phenotype
Gene Expression
Messenger RNA

Keywords

  • Angiopoietin-1
  • Endothelial cell
  • MicroRNA
  • Phosphoinositide-3-kinase

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

The miR-126 regulates Angiopoietin-1 signaling and vessel maturation by targeting p85β. / Sessa, Roberto; Seano, Giorgio; di Blasio, Laura; Gagliardi, Paolo Armando; Isella, Claudio; Medico, Enzo; Cotelli, Franco; Bussolino, Federico; Primo, Luca.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1823, No. 10, 10.2012, p. 1925-1935.

Research output: Contribution to journalArticle

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