MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A
| Autor: | Andreas M. Zeiher, Angelika Bonauer, Jes Niels Boeckel, Andrea Knau, Jens Kroll, Timo Frömel, Eduard Hergenreider, Reinier A. Boon, Katrin Bennewitz, Stefanie Dimmeler, David Kaluza, Ingrid Fleming, Carmen Urbich, Carmen Doebele |
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| Přispěvatelé: | Physiology |
| Rok vydání: | 2012 |
| Předmět: |
Embryo
Nonmammalian Cell Survival Angiogenesis Blotting Western Immunology Gene Expression Neovascularization Physiologic Semaphorins Biology Transfection Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Vasculogenesis Semaphorin Human Umbilical Vein Endothelial Cells Animals Humans 3' Untranslated Regions Cells Cultured Zebrafish 030304 developmental biology 0303 health sciences Matrigel Reverse Transcriptase Polymerase Chain Reaction Endothelial Cells Cell Biology Hematology Embryonic stem cell Angiogenesis inhibitor Cell biology Mice Inbred C57BL Endothelial stem cell Vascular endothelial growth factor B MicroRNAs HEK293 Cells 030220 oncology & carcinogenesis Blood Vessels RNA Interference |
| Zdroj: | 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 & 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 Blood, 119(6), 1607-1618. American Society of Hematology Blood |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2011-08-373886 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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