Nuclear Factor of Activated T Cells Is Activated in the Endothelium of Retinal Microvessels in Diabetic Mice
Joint Authors
Gomez, Maria F.
Zetterqvist, Anna V.
Blanco, Fabiana
Öhman, Jenny
Berglund, Lisa M.
de Frutos Garcia, Sergio
Al-Naemi, Raed
Wigren, Maria
McGuire, Paul G.
Gonzalez Bosc, Laura V.
Kotova, Olga
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-03-31
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
The pathogenesis of diabetic retinopathy (DR) remains unclear but hyperglycemia is an established risk factor.
Endothelial dysfunction and changes in Ca2+ signaling have been shown to precede the onset of DR.
We recently demonstrated that high extracellular glucose activates the Ca2+/calcineurin-dependent transcription factor NFAT in cerebral arteries and aorta, promoting the expression of inflammatory markers.
Here we show, using confocal immunofluorescence, that NFAT is expressed in the endothelium of retinal microvessels and is readily activated by high glucose.
This was inhibited by the NFAT blocker A-285222 as well as by the ectonucleotidase apyrase, suggesting a mechanism involving the release of extracellular nucleotides.
Acute hyperglycemia induced by an IP-GTT (intraperitoneal glucose tolerance test) resulted in increased NFATc3 nuclear accumulation and NFAT-dependent transcriptional activity in retinal vessels of NFAT-luciferase reporter mice.
In both Akita (Ins2+/−) and streptozotocin- (STZ-) induced diabetic mice, NFAT transcriptional activity was elevated in retinal vessels.
In vivo inhibition of NFAT with A-285222 decreased the expression of OPN and ICAM-1 mRNA in retinal vessels, prevented a diabetes driven downregulation of anti-inflammatory IL-10 in retina, and abrogated the increased vascular permeability observed in diabetic mice.
Results identify NFAT signaling as a putative target for treatment of microvascular complications in diabetes.
American Psychological Association (APA)
Zetterqvist, Anna V.& Blanco, Fabiana& Öhman, Jenny& Kotova, Olga& Berglund, Lisa M.& de Frutos Garcia, Sergio…[et al.]. 2015. Nuclear Factor of Activated T Cells Is Activated in the Endothelium of Retinal Microvessels in Diabetic Mice. Journal of Diabetes Research،Vol. 2015, no. 2015, pp.1-14.
https://search.emarefa.net/detail/BIM-1067907
Modern Language Association (MLA)
Zetterqvist, Anna V.…[et al.]. Nuclear Factor of Activated T Cells Is Activated in the Endothelium of Retinal Microvessels in Diabetic Mice. Journal of Diabetes Research No. 2015 (2015), pp.1-14.
https://search.emarefa.net/detail/BIM-1067907
American Medical Association (AMA)
Zetterqvist, Anna V.& Blanco, Fabiana& Öhman, Jenny& Kotova, Olga& Berglund, Lisa M.& de Frutos Garcia, Sergio…[et al.]. Nuclear Factor of Activated T Cells Is Activated in the Endothelium of Retinal Microvessels in Diabetic Mice. Journal of Diabetes Research. 2015. Vol. 2015, no. 2015, pp.1-14.
https://search.emarefa.net/detail/BIM-1067907
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1067907