CpG preconditioning regulates miRNA expression that modulates genomic reprogramming associated with neuroprotection against ischemic injury.
Cytosine-phosphate-guanine (CpG) preconditioning reprograms the genomic response to stroke to protect the brain against ischemic injury. The mechanisms underlying genomic reprogramming are incompletely understood. MicroRNAs (miRNAs) regulate gene expression; however, their role in modulating gene responses produced by CpG preconditioning is unknown. We evaluated brain miRNA expression in response to CpG preconditioning before and after stroke using microarray. Importantly, we have data from previous gene microarrays under the same conditions, which allowed integration of miRNA and gene expression data to specifically identify regulated miRNA gene targets. CpG preconditioning did not significantly alter miRNA expression before stroke, indicating that miRNA regulation is not critical for the initiation of preconditioning-induced neuroprotection. However, after stroke, differentially regulated miRNAs between CpG- and saline-treated animals associated with the upregulation of several neuroprotective genes, implicating these miRNAs in genomic reprogramming that increases neuroprotection. Statistical analysis revealed that the miRNA targets were enriched in the gene population regulated in the setting of stroke, implying that miRNAs likely orchestrate this gene expression. These data suggest that miRNAs regulate endogenous responses to stroke and that manipulation of these miRNAs may have the potential to acutely activate novel neuroprotective processes that reduce damage.
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, USA.
Keri B
KB
Vartanian
Pacific Northwest National Laboratory, Richland, Washington, USA.
Hugh D
HD
Mitchell
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, USA.
Susan L
SL
Stevens
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, USA.
Valerie K
VK
Conrad
Pacific Northwest National Laboratory, Richland, Washington, USA.
Jason E
JE
McDermott
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, USA.
Mary P
MP
Stenzel-Poore
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D035683:MicroRNAs; D018696:Neuroprotective Agents; D009838:Oligodeoxyribonucleotides