CpG preconditioning regulates miRNA expression that modulates genomic reprogramming associated with neuroprotection against ischemic injury

Keri B. Vartanian, Hugh D. Mitchell, Susan L. Stevens, Valerie K. Conrad, Jason E. McDermott, Mary Stenzel-Poore

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)257-266
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume35
Issue number2
DOIs
StatePublished - Feb 2 2015

Fingerprint

Cytosine
Guanine
MicroRNAs
Phosphates
Wounds and Injuries
Stroke
Genes
Gene Expression
Neuroprotection
Brain
Up-Regulation

Keywords

  • microRNA
  • neuroprotection
  • preconditioning
  • reprogramming
  • stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

Cite this

CpG preconditioning regulates miRNA expression that modulates genomic reprogramming associated with neuroprotection against ischemic injury. / Vartanian, Keri B.; Mitchell, Hugh D.; Stevens, Susan L.; Conrad, Valerie K.; McDermott, Jason E.; Stenzel-Poore, Mary.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 35, No. 2, 02.02.2015, p. 257-266.

Research output: Contribution to journalArticle

Vartanian, Keri B. ; Mitchell, Hugh D. ; Stevens, Susan L. ; Conrad, Valerie K. ; McDermott, Jason E. ; Stenzel-Poore, Mary. / CpG preconditioning regulates miRNA expression that modulates genomic reprogramming associated with neuroprotection against ischemic injury. In: Journal of Cerebral Blood Flow and Metabolism. 2015 ; Vol. 35, No. 2. pp. 257-266.
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