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
Urbich, Carmen ; Kaluza, David ; Frömel, Timo ; Knau, Andrea ; Bennewitz, Katrin ; Boon, Reinier A. ; Bonauer, Angelika ; Doebele, Carmen ; Boeckel, Jes Niels ; Hergenreider, Eduard ; Zeiher, Andreas M. ; Kroll, Jens ; Fleming, Ingrid ; Dimmeler, Stefanie. / MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A. In: Blood. 2012 ; Vol. 119, No. 6. pp. 1607-1618.
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title = "MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A",
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.",
author = "Carmen Urbich and David Kaluza and Timo Fr{\"o}mel and Andrea Knau and Katrin Bennewitz and Boon, {Reinier A.} and Angelika Bonauer and Carmen Doebele and Boeckel, {Jes Niels} and Eduard Hergenreider and Zeiher, {Andreas M.} and Jens Kroll and Ingrid Fleming and Stefanie Dimmeler",
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Urbich, C, Kaluza, D, Frömel, T, Knau, A, Bennewitz, K, Boon, RA, Bonauer, A, Doebele, C, Boeckel, JN, Hergenreider, E, Zeiher, AM, Kroll, J, Fleming, I & Dimmeler, S 2012, 'MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A' Blood, vol. 119, no. 6, pp. 1607-1618. https://doi.org/10.1182/blood-2011-08-373886

MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A. / Urbich, Carmen; Kaluza, David; Frömel, Timo; Knau, Andrea; Bennewitz, Katrin; Boon, Reinier A.; Bonauer, Angelika; Doebele, Carmen; Boeckel, Jes Niels; Hergenreider, Eduard; Zeiher, Andreas M.; Kroll, Jens; Fleming, Ingrid; Dimmeler, Stefanie.

In: Blood, Vol. 119, No. 6, 09.02.2012, p. 1607-1618.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A

AU - Urbich, Carmen

AU - Kaluza, David

AU - Frömel, Timo

AU - Knau, Andrea

AU - Bennewitz, Katrin

AU - Boon, Reinier A.

AU - Bonauer, Angelika

AU - Doebele, Carmen

AU - Boeckel, Jes Niels

AU - Hergenreider, Eduard

AU - Zeiher, Andreas M.

AU - Kroll, Jens

AU - Fleming, Ingrid

AU - Dimmeler, Stefanie

PY - 2012/2/9

Y1 - 2012/2/9

N2 - 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.

AB - 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.

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U2 - 10.1182/blood-2011-08-373886

DO - 10.1182/blood-2011-08-373886

M3 - Article

VL - 119

SP - 1607

EP - 1618

JO - Blood

JF - Blood

SN - 0006-4971

IS - 6

ER -