ApoE and miR-146 in inflammation and atherosclerosis (Mus musculus)

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1LipopolysaccharidePU.1p65ApoEIrak1Tlr2Tlr4Mir146Traf6Nfkb2ox-LDLPp65PNfkb2Monocyte and macrophage activationpri-miR-146apre-miR-146apre-miR-146acytokine genes


Apolipoprotein E (ApoE) enhances purine-rich PU-box-binding protein 1 (PU.1)-dependent miR-146a transcription to suppress nuclear factor-κB (NF-κB)-driven monocyte and macrophage activation and thereby inflammation and atherosclerosis.

Environmental ligands of toll-like receptors (TLRs), including lipopolysaccharide (LPS) and oxidized low-density lipoprotein (oxLDL), caused by hyperlipidemia provoke inflammatory signaling in monocytes and macrophages resulting in NF-κB activation. Gene transcription from NF-κB activity results in the production of inflammatory mediators, including proatherogenic cytokines. It also results in the production of primary miR-146a (pri-miR-146a) that is subsequently processed into mature miR-146a that silences the expression of key TLR-adaptor molecules interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6). The production of miR-146a thereby serves as a regulatory feedback loop to suppress NF-κB activity and resolve inflammation. Findings from our study identified that cellular apoE expression contributes to amplify this regulatory feedback loop by increasing PU.1-dependent transcription of pri-miR-146a and thereby mature miR-146a production.

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  1. Li K, Ching D, Luk FS, Raffai RL; ''Apolipoprotein E enhances microRNA-146a in monocytes and macrophages to suppress nuclear factor-κB-driven inflammation and atherosclerosis.''; Circ Res, 2015 PubMed Europe PMC Scholia


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94329view20:54, 1 September 2017Khanspersupdated xref
89801view11:31, 6 October 2016Mkutmonfixed special characters in description
89132view21:48, 22 August 2016AriuttaOntology Term : 'disease pathway' added !
87398view11:05, 22 July 2016MaintBotadded missing graphids
84852view21:41, 28 March 2016Khanspersupdated interactions
84084view10:36, 13 January 2016EgonwAdded IDs for two metabolites.
84081view00:04, 13 January 2016Khansperschanged interaction types
83897view00:39, 23 December 2015Khansperschanged interaction types
83896view00:36, 23 December 2015KhanspersModified description
83895view00:35, 23 December 2015Khanspersremoved miR locus
83866view00:19, 18 December 2015KhanspersAdjusted state position
83865view00:18, 18 December 2015KhanspersAdded literature reference
83864view00:15, 18 December 2015KhanspersModified description
83862view21:13, 17 December 2015KhanspersNew pathway
83863view21:13, 17 December 2015KhanspersModified title

External references


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NameTypeDatabase referenceComment
ApoEGeneProductENSMUSG00000002985 (Ensembl)
Irak1GeneProductENSMUSG00000031392 (Ensembl)
LipopolysaccharideMetaboliteCHEBI:16412 (ChEBI)
Mir146GeneProductMI0000170 (miRBase Sequence)
Nfkb2GeneProductENSMUSG00000025225 (Ensembl)
PU.1GeneProduct20375 (Entrez Gene)
Tlr2GeneProductENSMUSG00000027995 (Ensembl)
Tlr4GeneProductENSMUSG00000039005 (Ensembl)
Traf6GeneProductENSMUSG00000027164 (Ensembl)
ox-LDLMetaboliteCHEBI:60151 (ChEBI)
p65GeneProductENSMUSG00000024927 (Ensembl)

Annotated Interactions

No annotated interactions

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