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Publication : TLR4/NF-κB-responsive microRNAs and their potential target genes: a mouse model of skeletal muscle ischemia-reperfusion injury.

First Author  Yang JC Year  2015
Journal  Biomed Res Int Volume  2015
Pages  410721 PubMed ID  25692136
Mgi Jnum  J:315359 Mgi Id  MGI:6830215
Doi  10.1155/2015/410721 Citation  Yang JC, et al. (2015) TLR4/NF-kappaB-responsive microRNAs and their potential target genes: a mouse model of skeletal muscle ischemia-reperfusion injury. Biomed Res Int 2015:410721
abstractText  BACKGROUND: The aim of this study was to profile TLR4/NF-kappaB-responsive microRNAs (miRNAs) and their potential target genes in the skeletal muscles of mice following ischemia-reperfusion injury. METHODS: Thigh skeletal muscles of C57BL/6, Tlr4(-/-), and NF-kappaB(-/-) mice isolated based on femoral artery perfusion were subjected to ischemia for 2 h and reperfusion for 0 h, 4 h, 1 d, and 7 d. The muscle specimens were analyzed with miRNA arrays. Immunoprecipitation with an argonaute 2- (Ago2-) specific monoclonal antibody followed by whole genome microarray was performed to identify mRNA associated with the RNA-silencing machinery. The potential targets of each upregulated miRNA were identified by combined analysis involving the bioinformatics algorithm miRanda and whole genome expression. RESULTS: Three TLR4/NF-kappaB-responsive miRNAs (miR-15a, miR-744, and miR-1196) were significantly upregulated in the muscles following ischemia-reperfusion injury. The combined in silico and whole genome microarray approaches identified 5, 4, and 20 potential target genes for miR-15a, miR-744, and miR-1196, respectively. Among the 3 genes (Zbed4, Lrsam1, and Ddx21) regulated by at least 2 of the 3 upregulated miRNAs, Lrsam1 and Ddx21 are known to be associated with the innate immunity pathway. CONCLUSIONS: This study profiled TLR4/NF-kappaB-responsive miRNAs and their potential target genes in mouse skeletal muscle subjected to ischemia-reperfusion injury.
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