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@ARTICLE{Demolli:126419,
author = {S. Demolli and C. Doebele and A. Doddaballapur and V. Lang
and B. Fisslthaler and E. Chavakis and M. Vinciguerra and S.
Sciacca and R. Henschler and M. Hecker and S. Savant and H.
Augustin$^*$ and D. Kaluza and S. Dimmeler and R. A. Boon},
title = {{M}icro{RNA}-30 mediates anti-inflammatory effects of shear
stress and {KLF}2 via repression of angiopoietin 2.},
journal = {Journal of molecular and cellular cardiology},
volume = {88},
issn = {0022-2828},
address = {New York, NY [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2017-02448},
pages = {111 - 119},
year = {2015},
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.},
keywords = {C11orf2 protein, human (NLM Chemicals) / E-Selectin (NLM
Chemicals) / ICAM1 protein, human (NLM Chemicals) / KLF2
protein, human (NLM Chemicals) / Kruppel-Like Transcription
Factors (NLM Chemicals) / MIRN30 microRNA, human (NLM
Chemicals) / MicroRNAs (NLM Chemicals) / RNA, Messenger (NLM
Chemicals) / SELE protein, human (NLM Chemicals) / Tumor
Necrosis Factor-alpha (NLM Chemicals) / Vascular Cell
Adhesion Molecule-1 (NLM Chemicals) / Vesicular Transport
Proteins (NLM Chemicals) / Intercellular Adhesion Molecule-1
(NLM Chemicals)},
cin = {A190},
ddc = {610},
cid = {I:(DE-He78)A190-20160331},
pnm = {321 - Basic Concepts (POF3-321)},
pid = {G:(DE-HGF)POF3-321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26456066},
doi = {10.1016/j.yjmcc.2015.10.009},
url = {https://inrepo02.dkfz.de/record/126419},
}