MicroRNA-532 regulates pericyte function through targeting the transcription regulator BACH1 and Angiopoietin-1

Sadie Slater, Eva Jover , Andrea Martello, Iker Rodriguez-Arabaolaza, Valeria Vincenza Alvino, Simon Satchell, Paolo Madeddu, Gaia Spinetti, Andrea Caporali, Rosa Vono, Tijana Mitić

Research output: Contribution to journalArticle (Academic Journal)

3 Citations (Scopus)
166 Downloads (Pure)

Abstract

MicroRNAs regulate endothelial function and angiogenesis, but their implication in pericyte biology remains undetermined. A PCR array, covering a panel of 379 human microRNAs, showed microRNA-532-5p to be one of the most differentially modulated by hypoxia, which was confirmed by qPCR in both skeletal muscle and adventitial pericytes. Furthermore, microRNA-532-5p was upregulated in murine muscular pericytes early after experimentally induced ischemia, decreasing below baseline after reperfusion. Transfection of human pericytes with anti-microRNA, microRNA-mimic, or controls indicates microRNA-532-5p modulates pro-angiogenic activity via transcriptional regulation of angiopoietin-1. Tie-2 blockade abrogated the ability of microRNA-532-5p-overexpressing pericytes to promote endothelial network formation in vitro. However, angiopoietin-1 is not a direct target of microRNA-532-5p. In silico analysis of microRNA-532-5p inhibitory targets associated with angiopoietin-1 transcription indicated three potential candidates, BACH1, HIF1AN, and EGLN1. Binding of microRNA-532-5p to the BACH1 3′ UTR was confirmed by luciferase assay. MicroRNA-532-5p silencing increased BACH1, while a microRNA-532-5p mimic decreased expression. Silencing of BACH1 modulated angiopoietin-1 gene and protein expression. ChIP confirmed BACH1 transcriptional regulation of angiopoietin-1 promoter. Finally, microRNA-532-5p overexpression increased pericyte coverage in an in vivo Matrigel assay, suggesting its role in vascular maturation. This study provides a new mechanistic understanding of the transcriptional program orchestrating angiopoietin-1/Tie-2 signaling in human pericytes.
Original languageEnglish
Number of pages15
JournalMolecular Therapy
Early online date1 Sep 2018
DOIs
Publication statusE-pub ahead of print - 1 Sep 2018

Keywords

  • angiogenesis
  • pericytes
  • microRNA

Fingerprint Dive into the research topics of 'MicroRNA-532 regulates pericyte function through targeting the transcription regulator BACH1 and Angiopoietin-1'. Together they form a unique fingerprint.

  • Projects

    NIHR BRC Cardiovascular

    Angelini, G. D.

    1/04/1731/03/22

    Project: Research, Parent

    Cite this