ApoE and miR-146 in inflammation and atherosclerosis (Homo sapiens)

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12LipopolysaccharideHDLTLR2MIR146ARELASPI1TRAF6NFKB2IRAK1APOETLR4ox-LDLPRELANFKB2PMonocyte and macrophage activationpri-miR-146apre-miR-146apre-miR-146acytokine genesHDL


Description

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.

Comments

HomologyMapper 
This pathway was inferred from Mus musculus pathway "ApoE and miR-146 in inflammation and atherosclerosis", WP3592 revision 89801, with a 90.0% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

  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
  2. Raffai RL; ''MicroRNA-146a& hematopoiesis: friend or foe in atherosclerosis.''; Noncoding RNA Investig, 2018 PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
106298view17:42, 20 August 2019KhanspersModified description
105530view06:01, 9 August 2019KhanspersModified description
103750view22:34, 3 April 2019Khanspersupdated xref for mir-146
103697view21:05, 28 March 2019KhanspersCorrected TRAF6 and added APOE/HDL elimination connection
97678view13:14, 1 June 2018AMTanOntology Term : 'atherosclerosis' added !
90739view23:28, 13 December 2016Khanspersupdated link to source pathway
90732view23:15, 13 December 2016KhanspersOntology Term : 'disease pathway' added !
90731view23:14, 13 December 2016KhanspersNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
APOEGeneProductENSG00000130203 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000002985
HDLMetaboliteCHEBI:39025 (ChEBI)
IRAK1GeneProductENSG00000184216 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000031392
LipopolysaccharideMetaboliteCHEBI:16412 (ChEBI)
MIR146AGeneProductENSG00000283733 (Ensembl) No homologues found for original id Mb:MI0000170
NFKB2GeneProductENSG00000077150 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000025225
RELAGeneProductENSG00000173039 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000024927
SPI1GeneProductENSG00000066336 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:20375
TLR2GeneProductENSG00000137462 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000027995
TLR4GeneProductENSG00000136869 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000039005
TRAF6GeneProductENSG00000175104 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000017386
ox-LDLMetaboliteCHEBI:60151 (ChEBI)

Annotated Interactions

No annotated interactions
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