Shear stress-regulated miR-27b controls pericyte recruitment by repressing SEMA6A and SEMA6D

• Verfasst von: Demolli, Shemsi [VerfasserIn]
• Verfasst von: Korff, Thomas [VerfasserIn]
• Verfasst von: Hecker, Markus [VerfasserIn]
• Titel: Shear stress-regulated miR-27b controls pericyte recruitment by repressing SEMA6A and SEMA6D
• Verf.angabe: Shemsi Demolli, Anuradha Doddaballapur, Kavi Devraj, Konstantin Stark, Yosif Manavski, Annekathrin Eckart, Christoph M. Zehendner, Tina Lucas, Thomas Korff, Markus Hecker, Steffen Massberg, Stefan Liebner, David Kaluza, Reinier A. Boon, and Stefanie Dimmeler
• E-Jahr: 2017
• Jahr: 2017 May 1
• Umfang: 11 S.
• Teil: volume:113
• Teil: year:2017
• Teil: number:6
• Teil: pages:681-691
• Teil: extent:11
• Fussnoten: Gesehen am 22.10.2018
• Titel Quelle: Enthalten in: Cardiovascular research
• Ort Quelle: Oxford : Oxford University Press, 1967
• Jahr Quelle: 2017
• Band/Heft Quelle: 113(2017), 6, Seite 681-691
• ISSN Quelle: 1755-3245
• DOI: doi:10.1093/cvr/cvx032
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1582170118

Abstract

Aims: Vessel maturation involves the recruitment of mural cells such as pericytes and smooth muscle cells. Laminar shear stress is a major trigger for vessel maturation, but the molecular mechanisms by which shear stress affects recruitment of pericytes are unclear. MicroRNAs (miRs) are small non-coding RNAs, which post-transcriptionally control gene expression. The aim of the present study was to unveil the mechanism by which shear stress-regulated microRNAs contribute to vessel maturation. Methods and results: Here, we show that laminar shear stress increased miR-27a and miR-27b expression in vitro and in ex vivo in mouse femoral artery explants. Overexpression of miR-27b in endothelial cells increased pericyte adhesion and pericyte recruitment in vitro. In vitro barrier function of endothelial–pericyte co-cultures was augmented by miR-27b overexpression, whereas inhibition of miR-27a/b reduced adhesion and pericyte coverage and decreased barrier functions. In vivo, pharmacological inhibition of miR-27a/b by locked nucleic acid antisense oligonucleotides significantly reduced pericyte coverage and increased water content in the murine uterus. MiR-27b overexpression repressed semaphorins (SEMA), which mediate repulsive signals, and the vessel destabilizing human but not mouse Angiopoietin-2 (Ang-2). Silencing of SEMA6A and SEMA6D rescued the reduced pericyte adhesion by miR-27 inhibition. Furthermore, inhibition of SEMA6D increased barrier function of an endothelial–pericyte co-culture in vitro. Conclusion: The present study demonstrates for the first time that shear stress-regulated miR-27b promotes the interaction of endothelial cells with pericytes, partly by repressing SEMA6A and SEMA6D.