RGD Reference Report - Oxysterol and diabetes activate STAT3, and control endothelial expression of profilin-1 via OSBP1. - Rat Genome Database

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Oxysterol and diabetes activate STAT3, and control endothelial expression of profilin-1 via OSBP1.

Authors: Romeo, GR  Kazlauskas, A 
Citation: Romeo GR and Kazlauskas A, J Biol Chem. 2008 Jan 28;.
RGD ID: 2291921
Pubmed: PMID:18230613   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M710092200   (Journal Full-text)

Endothelial dysfunction plays a central role in diabetic vascular disease but its molecular bases are not completely defined. We showed previously that the actin-binding protein proflin-1 was increased in the diabetic endothelium and that attenuated expression of profilin-1 protected from atherosclerosis. Also, 7-ketocholesterol upregulated profilin-1 in endothelial cells via transcriptional mechanisms. The present study addressed the pathways responsible for profilin-1 gene expression in 7ketocholesterol-stimulated endothelial cells and in the diabetic aorta. In luciferase reporter assays, the response to 7-ketocholesterol within the 5'-flanking region of profilin-1 was dependent on a single STAT-response element. In aortic endothelial cells, 7-ketocholesterol enhanced STAT3 activation, which required JAK-2 and tyrosine 394 phosphorylation of oxysterol-binding protein-1. These changes were recapitulated in the aorta of diabetic rats. Also, 7-ketocholesterol in cultured endothelial cells and diabetes in the aorta elicited the recruitment of STAT3, and relevant coregulatory factors to the oxysterol-responsive region of the profilin-1 promoter. These events were required for profilin-1 upregulation. These studies identify a previously unrecognized oxysterol-binding protein-mediated mode of activation of STAT3, which controls the expression of the pro-atherogenic protein profilin-1 in response to 7-ketocholesterol and the diabetic milieu.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
OSBPHumanExperimental Diabetes Mellitus  ISOOsbp (Rattus norvegicus)protein:increased tyrosine phosphorylation:aortaRGD 
OsbpRatExperimental Diabetes Mellitus  IDA protein:increased tyrosine phosphorylation:aortaRGD 
OsbpMouseExperimental Diabetes Mellitus  ISOOsbp (Rattus norvegicus)protein:increased tyrosine phosphorylation:aortaRGD 
STAT3HumanExperimental Diabetes Mellitus  ISOStat3 (Rattus norvegicus)protein:increased tyrosine phosphorylation:aorta endotheliumRGD 
Stat3RatExperimental Diabetes Mellitus  IEP protein:increased tyrosine phosphorylation:aorta endotheliumRGD 
Stat3MouseExperimental Diabetes Mellitus  ISOStat3 (Rattus norvegicus)protein:increased tyrosine phosphorylation:aorta endotheliumRGD 


Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
OsbpRatpositive regulation of protein modification process  IMP tyrosine phosphorylation of STAT proteinRGD 


Genes (Rattus norvegicus)
Osbp  (oxysterol binding protein) Stat3  (signal transducer and activator of transcription 3)

Genes (Mus musculus)
Osbp  (oxysterol binding protein) Stat3  (signal transducer and activator of transcription 3)

Genes (Homo sapiens)
OSBP  (oxysterol binding protein) STAT3  (signal transducer and activator of transcription 3)