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Series GSE12696 Query DataSets for GSE12696
Status Public on Aug 31, 2010
Title Apoptotic bodies unleash functional CXCL12 expression through microRNA-126
Platform organisms Homo sapiens; Mus musculus; Rattus norvegicus
Sample organism Homo sapiens
Experiment type Non-coding RNA profiling by array
Summary Apoptosis plays a pivotal role in embryogenesis and postnatal cell homeostasis, involving DNA or subcellular fragmentation, and shedding of small membranous microvesicles termed apoptotic bodies (AB). Following DNA damage, hypoxia, or vascular injury, the chemokine CXCL12 has been implicated in the recruitment of progenitor cells for tissue regeneration through its receptor CXCR4 and in mechanisms counteracting apoptosis. Whether AB deliver alarm signals for regenerative responses to neighbouring cells beyond recruitment or eat-me signals for phagocytes and relevance to diseases with abundant apoptosis, eg atherosclerosis, remains unknown. Here we show that endothelial cell-derived AB are generated during diet-induced atherosclerosis and can be transferred to recipient endothelial or smooth muscle cells to induce functional expression of CXCL12. This is mediated through miRNA-126 enriched in AB, which acts by silencing RGS16 translation and unlocking CXCR4 to unleash an auto-regulatory feedback loop inducing CXCL12. Injection of AB promoted mobilization and incorporation of progenitor cells, reducing diet-induced atherosclerosis in apolipoprotein E-deficient mice, and local transfer of microRNA-126 inhibited collar-induced arterial plaque formation. This was associated with increased smooth muscle content but decreased macrophage and apoptotic cell content, all features of plaque stability. Our data identify a new mechanism, by which AB confer microRNA-126 as a paracrine alarm messenger to enhance CXCR4 signals and CXCL12 expression, thereby limiting or repairing vascular damage. This adds to the important functions of microRNAs in health and disease and may extend to progenitor cell recruitment during other forms of tissue repair or homeostasis.
 
Overall design AB were isolated from super­natants of apoptotic, serum-starved human umbilical vein endothelial cells (HUVECs) by sequential centrifugation steps. Total RNA was isolated from AB or HUVECs and microRNA was purified using the mirVanaTM miRNA Isolation Kit (Ambion). microRNA obtained from 10 µg of total RNA was labeled using the mirVanaTM miRNA Labeling Kit (Ambion) and fluorescent Cy3 (Molecular Probes), and hybridized to the Ambion mirVanaTM miRNA Bioarray (1566 v.1). Hybridized mirVana miRNA Bioarrays were scanned and quantified by using ImaGene 5.5.4 (Bio Discovery). Resulted signal intensities were background corrected and then normalized using variance stabilization normalization. (Huber, 2002).
 
Contributor(s) Zernecke A, Bidzhekov K, Noels H, Gan L, Denecke B, Shagdarsuren E, Hristov M, Weber C
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Submission date Sep 08, 2008
Last update date Mar 20, 2012
Contact name Lin Gan
Organization name University Hospital Aachen
Department IZKF
Lab Genomics facility
Street address Pauwelsstr. 30
City Aachen
ZIP/Postal code 52074
Country Germany
 
Platforms (1)
GPL3444 Ambion Human_Mouse_Rat mirVana miRNA Bioarray_1566V1
Samples (2)
GSM318679 Human umbilical vein endothelial cells
GSM318680 Apoptotic bodies
Relations
BioProject PRJNA112707

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE12696_RAW.tar 230.0 Kb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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