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  • Zetterqvist, AnnaLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Diabetiska komplikationer,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Diabetic Complications (author)

Nuclear Factor of Activated T Cells Is Activated in the Endothelium of Retinal Microvessels in Diabetic Mice.

  • Article/chapterEnglish2015

Publisher, publication year, extent ...

  • Hindawi Limited,2015
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:f6fd755b-05e6-4820-997b-0219ad7f964f
  • https://lup.lub.lu.se/record/5337648URI
  • https://doi.org/10.1155/2015/428473DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • The pathogenesis of diabetic retinopathy (DR) remains unclear but hyperglycemia is an established risk factor. Endothelial dysfunction and changes in Ca(2+) signaling have been shown to precede the onset of DR. We recently demonstrated that high extracellular glucose activates the Ca(2+)/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.

Subject headings and genre

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  • Blanco, FabianaLund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups(Swepub:lu)med-fbc (author)
  • Öhman, JennyLund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Diabetiska komplikationer,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Diabetic Complications(Swepub:lu)mphy-jni (author)
  • Kotova, OlgaLund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups(Swepub:lu)med-oak (author)
  • Berglund, LisaLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Diabetiska komplikationer,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Diabetic Complications(Swepub:lu)mphy-lni (author)
  • de Frutos Garcia, Sergio (author)
  • Al-Naemi, RaedLund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups(Swepub:lu)med-rai (author)
  • Wigren, MariaLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups(Swepub:lu)med-mbr (author)
  • McGuire, Paul G (author)
  • Gonzalez Bosc, Laura V (author)
  • Gomez, MariaLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Diabetiska komplikationer,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Diabetic Complications(Swepub:lu)mphy-mgo (author)
  • Kardiovaskulär forskning - immunitet och aterosklerosForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:Journal of Diabetes Research: Hindawi Limited20152314-67532314-6745

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