RGD Reference Report - MicroRNA 146a (miR-146a) is over-expressed during prion disease and modulates the innate immune response and the microglial activation state. - Rat Genome Database

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MicroRNA 146a (miR-146a) is over-expressed during prion disease and modulates the innate immune response and the microglial activation state.

Authors: Saba, Reuben  Gushue, Shantel  Huzarewich, Rhiannon L C H  Manguiat, Kathy  Medina, Sarah  Robertson, Catherine  Booth, Stephanie A 
Citation: Saba R, etal., PLoS One. 2012;7(2):e30832. doi: 10.1371/journal.pone.0030832. Epub 2012 Feb 17.
RGD ID: 126925151
Pubmed: PMID:22363497   (View Abstract at PubMed)
PMCID: PMC3281888   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0030832   (Journal Full-text)

Increasing evidence supports the involvement of microRNAs (miRNAs) in inflammatory and immune processes in prion neuropathogenesis. MiRNAs are small, non-coding RNA molecules which are emerging as key regulators of numerous cellular processes. We established miR-146a over-expression in prion-infected mouse brain tissues concurrent with the onset of prion deposition and appearance of activated microglia. Expression profiling of a variety of central nervous system derived cell-lines revealed that miR-146a is preferentially expressed in cells of microglial lineage. Prominent up-regulation of miR-146a was evident in the microglial cell lines BV-2 following TLR2 or TLR4 activation and also EOC 13.31 via TLR2 that reached a maximum 24-48 hours post-stimulation, concomitant with the return to basal levels of transcription of induced cytokines. Gain- and loss-of-function studies with miR-146a revealed a substantial deregulation of inflammatory response pathways in response to TLR2 stimulation. Significant transcriptional alterations in response to miR-146a perturbation included downstream mediators of the pro-inflammatory transcription factor, nuclear factor-kappa B (NF-κB) and the JAK-STAT signaling pathway. Microarray analysis also predicts a role for miR-146a regulation of morphological changes in microglial activation states as well as phagocytic mediators of the oxidative burst such as CYBA and NOS3. Based on our results, we propose a role for miR-146a as a potent modulator of microglial function by regulating the activation state during prion induced neurodegeneration.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
scrapie  ISOMir146 (Mus musculus)126925151; 126925151miRNA:increased expression:brain more ...RGD 
scrapie  IEP 126925151miRNA:increased expression:brain more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir146a  (microRNA 146a)

Genes (Mus musculus)
Mir146  (microRNA 146)

Genes (Homo sapiens)
MIR146A  (microRNA 146a)


Additional Information