TY  - JOUR
AU  - Demolli, Shemsi
AU  - Doebele, Carmen
AU  - Doddaballapur, Anuradha
AU  - Lang, Victoria
AU  - Fisslthaler, Beate
AU  - Chavakis, Emmanouil
AU  - Vinciguerra, Manlio
AU  - Sciacca, Sergio
AU  - Henschler, Reinhard
AU  - Hecker, Markus
AU  - Savant, Soniya
AU  - Augustin, Hellmut
AU  - Kaluza, David
AU  - Dimmeler, Stefanie
AU  - Boon, Reinier A
TI  - MicroRNA-30 mediates anti-inflammatory effects of shear stress and KLF2 via repression of angiopoietin 2.
JO  - Journal of molecular and cellular cardiology
VL  - 88
SN  - 0022-2828
CY  - New York, NY [u.a.]
PB  - Elsevier
M1  - DKFZ-2017-02448
SP  - 111 - 119
PY  - 2015
AB  - 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.
KW  - C11orf2 protein, human (NLM Chemicals)
KW  - E-Selectin (NLM Chemicals)
KW  - ICAM1 protein, human (NLM Chemicals)
KW  - KLF2 protein, human (NLM Chemicals)
KW  - Kruppel-Like Transcription Factors (NLM Chemicals)
KW  - MIRN30 microRNA, human (NLM Chemicals)
KW  - MicroRNAs (NLM Chemicals)
KW  - RNA, Messenger (NLM Chemicals)
KW  - SELE protein, human (NLM Chemicals)
KW  - Tumor Necrosis Factor-alpha (NLM Chemicals)
KW  - Vascular Cell Adhesion Molecule-1 (NLM Chemicals)
KW  - Vesicular Transport Proteins (NLM Chemicals)
KW  - Intercellular Adhesion Molecule-1 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26456066
DO  - DOI:10.1016/j.yjmcc.2015.10.009
UR  - https://inrepo02.dkfz.de/record/126419
ER  -