MicroRNA-30 mediates anti-inflammatory effects of shear stress and KLF2 via repression of angiopoietin 2

• Verfasst von: Demolli, Shemsi [VerfasserIn]
• Verfasst von: Savant, Soniya [VerfasserIn]
• Verfasst von: Hecker, Markus [VerfasserIn]
• Verfasst von: Augustin, Hellmut [VerfasserIn]
• Titel: MicroRNA-30 mediates anti-inflammatory effects of shear stress and KLF2 via repression of angiopoietin 2
• Verf.angabe: Shemsi Demolli, Carmen Doebele, Anuradha Doddaballapur, Victoria Lang, Beate Fisslthaler, Emmanouil Chavakis, Manlio Vinciguerra, Sergio Sciacca, Reinhard Henschler, Markus Hecker, Soniya Savant, Hellmut G. Augustin, David Kaluza, Stefanie Dimmeler, Reinier A. Boon
• E-Jahr: 2015
• Jahr: November 2015
• Umfang: 9 S.
• Fussnoten: Gesehen am 14.12.2017
• Titel Quelle: Enthalten in: Journal of molecular and cellular cardiology
• Ort Quelle: New York, NY [u.a.] : Elsevier, 1970
• Jahr Quelle: 2015
• Band/Heft Quelle: 88(2015), C, Suppl., Seite 111-119
• ISSN Quelle: 1095-8584
• DOI: doi:10.1016/j.yjmcc.2015.10.009
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Angiopoietin
• Sach-SW: Endothelial cell
• Sach-SW: KLF2
• Sach-SW: Laminar shear stress
• Sach-SW: MicroRNA
• K10plus-PPN: 1566399904

Abstract

MicroRNAs are endogenously expressed small noncoding RNAs that regulate gene expression. Laminar blood flow induces atheroprotective gene expression in endothelial cells (ECs) in part by upregulating the transcription factor KLF2. Here, we identified KLF2- and flow-responsive miRs that affect gene expression in ECs. Bioinformatic assessment of mRNA expression patterns identified the miR-30-5p seed sequence to be highly enriched in mRNAs that are downregulated by KLF2. Indeed, KLF2 overexpression and shear stress stimulation in vitro and in vivo increased the expression of miR-30-5p family members. Furthermore, we identified angiopoietin 2 (Ang2) as a target of miR-30. MiR-30 overexpression reduces Ang2 levels, whereas miR-30 inhibition by LNA-antimiRs induces Ang2 expression. Consistently, miR-30 reduced basal and TNF-α-induced expression of the inflammatory cell-cell adhesion molecules E-selectin, ICAM1 and VCAM1, which was rescued by stimulation with exogenous Ang2. In summary, KLF2 and shear stress increase the expression of the miR-30-5p family which acts in an anti-inflammatory manner in ECs by impairing the expression of Ang2 and inflammatory cell-cell adhesion molecules. The upregulation of miR-30-5p family members may contribute to the atheroprotective effects of shear stress.