MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A
- Authors
- Urbich, C., Kaluza, D., Frömel, T., Knau, A., Bennewitz, K., Boon, R.A., Bonauer, A., Doebele, C., Boeckel, J.N., Hergenreider, E., Zeiher, A.M., Kroll, J., Fleming, I., and Dimmeler, S.
- ID
- ZDB-PUB-120106-3
- Date
- 2012
- Source
- Blood 119(6): 1607-1616 (Journal)
- Registered Authors
- Kroll, Jens
- Keywords
- none
- MeSH Terms
-
- Animals
- Endothelial Cells/metabolism*
- Endothelial Cells/physiology
- Blood Vessels/embryology
- Blood Vessels/metabolism
- Zebrafish/embryology
- Zebrafish/genetics
- Humans
- Blotting, Western
- Reverse Transcriptase Polymerase Chain Reaction
- Semaphorins/genetics*
- Semaphorins/metabolism
- Mice
- Gene Expression
- Human Umbilical Vein Endothelial Cells/metabolism
- Human Umbilical Vein Endothelial Cells/physiology
- Neovascularization, Physiologic/genetics*
- Neovascularization, Physiologic/physiology
- Transfection
- Embryo, Nonmammalian/blood supply
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Cell Survival/genetics
- Cell Survival/physiology
- Cells, Cultured
- RNA Interference
- HEK293 Cells
- MicroRNAs/genetics*
- MicroRNAs/metabolism
- Mice, Inbred C57BL
- 3' Untranslated Regions/genetics
- PubMed
- 22184411 Full text @ Blood
MicroRNAs (miRs) are small RNAs that regulate gene expression at the post-transcriptional level. MiR-27 is expressed in endothelial cells but the specific function 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'UTR 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 neighbouring endothelial cells.