MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A

Carmen Urbich, David Kaluza, Timo Frömel, Andrea Knau, Katrin Bennewitz, Reinier A. Boon, Angelika Bonauer, Carmen Doebele, Jes Niels Boeckel, Eduard Hergenreider, Andreas M. Zeiher, Jens Kroll, Ingrid Fleming, Stefanie Dimmeler

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

MicroRNAs (miRs) are small RNAs that regulate gene expression at the posttranscriptional level. miR-27 is expressed in endothelial cells, but the specific functions of miR-27b and its family member miR-27a are largely unknown. Here we demonstrate that overexpression of miR-27a and miR-27b significantly increased endothelial cell sprouting. Inhibition of both miR-27a and miR-27b impaired endothelial cell sprout formation and induced endothelial cell repulsion in vitro. In vivo, inhibition of miR-27a/b decreased the number of perfused vessels in Matrigel plugs and impaired embryonic vessel formation in zebrafish. Mechanistically, miR-27 regulated the expression of the angiogenesis inhibitor semaphorin 6A (SEMA6A) in vitro and in vivo and targeted the 3′-untranslated region of SEMA6A. Silencing of SEMA6A partially reversed the inhibition of endothelial cell sprouting and abrogated the repulsion of endothelial cells mediated by miR-27a/b inhibition, indicating that SEMA6A is a functionally relevant miR-27 downstream target regulating endothelial cell repulsion. In summary, we show that miR-27a/b promotes angiogenesis by targeting the angiogenesis inhibitor SEMA6A, which controls repulsion of neighboring endothelial cells.

Original languageEnglish
Pages (from-to)1607-1618
Number of pages12
JournalBlood
Volume119
Issue number6
DOIs
Publication statusPublished - 9 Feb 2012

Cite this

Urbich, C., Kaluza, D., Frömel, T., Knau, A., Bennewitz, K., Boon, R. A., ... Dimmeler, S. (2012). MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A. Blood, 119(6), 1607-1618. https://doi.org/10.1182/blood-2011-08-373886