RGD Reference Report - Expression of lysophosphatidic acid, autotaxin and acylglycerol kinase as biomarkers in diabetic retinopathy. - Rat Genome Database

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Expression of lysophosphatidic acid, autotaxin and acylglycerol kinase as biomarkers in diabetic retinopathy.

Authors: Abu El-Asrar, AM  Mohammad, G  Nawaz, MI  Siddiquei, MM  Kangave, D  Opdenakker, G 
Citation: Abu El-Asrar AM, etal., Acta Diabetol. 2013 Jun;50(3):363-71. doi: 10.1007/s00592-012-0422-1. Epub 2012 Aug 4.
RGD ID: 9685437
Pubmed: PMID:22864860   (View Abstract at PubMed)
DOI: DOI:10.1007/s00592-012-0422-1   (Journal Full-text)

The proinflammatory lysophosphatidic acid (LPA) is a potent activator of several transcriptional factors and signaling pathways and a potent modulator of genes involved in inflammation, angiogenesis and fibrosis. This study was conducted to measure the levels of LPA and LPA-producing enzymes, autotaxin (ATX) and acylglycerol kinase (AGK) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the level of vascular endothelial growth factor (VEGF). In addition, we examined the expression of ATX, AGK and VEGF receptor-2 (VEGFR-2) in the retinas of diabetic rats. Vitreous samples from 42 PDR and 35 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Vitreous samples and retinas of rats were examined by Western blot analysis. VEGF, LPA and AGK levels in vitreous samples from PDR patients were significantly higher than those in control patients without diabetes (p < 0.001 for all comparisons). ATX levels in PDR with active neovascularization and inactive PDR were significantly lower than those in nondiabetic patients (p = 0.045). Mean VEGF and AGK levels in PDR with active neovascularization were significantly higher than those in inactive PDR and nondiabetic patients (p < 0.001 for both comparisons). A significant correlation was observed between levels of VEGF and levels of AGK in PDR patients (r = 0.954; p < 0.001). Western blot analysis revealed a significant increase in the expression of AGK and VEGFR-2 in vitreous samples and the retinas of diabetic rats compared to nondiabetic controls, whereas ATX was significantly downregulated. Our findings suggest that ATX-AGK-LPA signaling axis might be an important player in the development and progression of diabetic retinopathy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOEnpp2 (Rattus norvegicus)9685437; 9685437protein:decreased expression:retina:RGD 
Experimental Diabetes Mellitus  IEP 9685437protein:decreased expression:retina:RGD 
proliferative diabetic retinopathy disease_progressionIEP 9685437protein:decreased expression:vitreous:RGD 
proliferative diabetic retinopathy disease_progressionISOENPP2 (Homo sapiens)9685437; 9685437protein:decreased expression:vitreous:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Enpp2  (ectonucleotide pyrophosphatase/phosphodiesterase 2)

Genes (Mus musculus)
Enpp2  (ectonucleotide pyrophosphatase/phosphodiesterase 2)

Genes (Homo sapiens)
ENPP2  (ectonucleotide pyrophosphatase/phosphodiesterase 2)


Additional Information