Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection

Apoptosis is a pivotal process in embryogenesis and postnatal cell homeostasis and involves the shedding of membranous microvesicles termed apoptotic bodies. In response to tissue damage, the CXC chemokine CXCL12 and its receptor CXCR4 counteract apoptosis and recruit progenitor cells. Here, we show...

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Veröffentlicht in:Science signaling Jg. 2; H. 100; S. ra81
Hauptverfasser: Zernecke, Alma, Bidzhekov, Kiril, Noels, Heidi, Shagdarsuren, Erdenechimeg, Gan, Lin, Denecke, Bernd, Hristov, Mihail, Köppel, Thomas, Jahantigh, Maliheh Nazari, Lutgens, Esther, Wang, Shusheng, Olson, Eric N, Schober, Andreas, Weber, Christian
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 08.12.2009
Schlagworte:
Animals
Apoptosis - physiology
Atherosclerosis - pathology
Base Sequence
Chemokine CXCL12 - genetics
Chemokine CXCL12 - metabolism
Chemokine CXCL12 - physiology
Disease Models, Animal
DNA Primers
Endothelium, Vascular - cytology
Enzyme-Linked Immunosorbent Assay
Mice
MicroRNAs - administration & dosage
Receptors, CXCR4 - metabolism
Reverse Transcriptase Polymerase Chain Reaction
ISSN:1937-9145, 1937-9145
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Zusammenfassung:Apoptosis is a pivotal process in embryogenesis and postnatal cell homeostasis and involves the shedding of membranous microvesicles termed apoptotic bodies. In response to tissue damage, the CXC chemokine CXCL12 and its receptor CXCR4 counteract apoptosis and recruit progenitor cells. Here, we show that endothelial cell-derived apoptotic bodies are generated during atherosclerosis and convey paracrine alarm signals to recipient vascular cells that trigger the production of CXCL12. CXCL12 production was mediated by microRNA-126 (miR-126), which was enriched in apoptotic bodies and repressed the function of regulator of G protein (heterotrimeric guanosine triphosphate-binding protein) signaling 16, an inhibitor of G protein-coupled receptor (GPCR) signaling. This enabled CXCR4, a GPCR, to trigger an autoregulatory feedback loop that increased the production of CXCL12. Administration of apoptotic bodies or miR-126 limited atherosclerosis, promoted the incorporation of Sca-1+ progenitor cells, and conferred features of plaque stability on different mouse models of atherosclerosis. This study highlights functions of microRNAs in health and disease that may extend to the recruitment of progenitor cells during other forms of tissue repair or homeostasis.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1937-9145
1937-9145
DOI:10.1126/scisignal.2000610