Linked Life Data

20656888

Source:http://linkedlifedata.com/resource/pubmed/id/20656888

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-10-4
pubmed:abstractText
We have previously reported that preconditioning of bone marrow-derived mesenchymal stem cells (MSCs) with diazoxide (DZ) significantly improved cell survival via NF-?B signaling. Since micro-RNAs (miRNAs) are critical regulators of a wide variety of biological events, including apoptosis, proliferation, and differentiation, it is likely that DZ-induced survival is mediated by miRNAs. Here we show that miR-146a expressed during preconditioning with DZ is a key regulator of stem cell survival. Treatment of MSCs with DZ (200 ?M) markedly increased miR-146a expression and promoted cell survival, as evaluated by lactate dehydrogenase release and transferase-mediated dUTP nick-end labeling staining. Interestingly, blocking NF-?B by IKK-? NEMO binding domain inhibitor peptide did not induce miR-146a expression, indicating NF-?B regulates miR-146a expression. Moreover, blockade of miR-146a expression by antisense miR-146a inhibitor abolished DZ-induced cytoprotective effects, suggesting a critical role of miR-146a in MSC survival. Computational analysis found a consensus putative target site of miR-146a relevant to apoptosis in the 3' untranslated region of Fas mRNA. The role of Fas as a target gene was substantiated by abrogation of miR-146a, which markedly increased Fas protein expression. This was verified by luciferase reporter assay, which showed that forced expression of miR-146a downregulated Fas expression via targeting its 3'-UTR of this gene. Taken together, these data demonstrated that cytoprotection afforded by preconditioning of MSCs with DZ was regulated by miR-146a induction, which may be a novel therapeutic target in cardiac ischemic diseases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1522-1539
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H1077-82
pubmed:dateRevised
2011-10-3
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Diazoxide potentiates mesenchymal stem cell survival via NF-kappaB-dependent miR-146a expression by targeting Fas.
pubmed:affiliation
Department of Pathology and Lab Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural