Vitamin D receptor activation in a diabetic-like environment: Potential role in the activity of the endothelial pro-inflammatory and thioredoxin pathways

T. Zitman-Gal, E. Golan, J. Green, J. Bernheim, S. Benchetrit

Research output: Contribution to journalArticlepeer-review

Abstract

High blood and tissue concentrations of glucose and advanced glycation end products (AGEs) are thought to play an important role in the development of diabetic vascular complications. Thioredoxin interacting protein (TXNIP) is up-regulated in response to high levels of glucose and is an endogenous inhibitor of thioredoxin (TRX), and may play a contributory role in the occurrence of diabetic-related vascular diseases. Vitamin D inhibits endothelial proliferation and is a cardiovascular protective agent. The present study evaluated the impact of paricalcitol and calcitriol on the endothelial inflammatory and TXNIP pathways in cultured endothelial cells exposed to a diabetic-like environment. Fresh human umbilical vein cord endothelial cells (HUVEC) were treated for 24 h with 200 μg/ml AGE-HSA and 250 mg/dl glucose concentrations, with paricalcitol or calcitriol. IL6, IL8, NFκB (p50/p65), receptor of AGE (RAGE), TXNIP, and TRX expressions were evaluated at the levels of mRNA, protein, and TRX activity. Calcitriol and paricalcitol significantly down-regulated the markers involved in the inflammatory responses. Only paricalcitol induced a significant decrease in TXNIP mRNA and protein expressions. Neither paricalcitol nor calcitriol affected TRX reductase activity or TRX mRNA and protein expressions. Our findings indicate that in an endothelial diabetic-like environment, paricalcitol and calcitriol significantly decreased the expression of genes involved in the inflammatory pathway. In this in vitro study, it seems that the TRX antioxidant system was not involved. The different effects found between paricalcitol and calcitriol might reflect the selectivity of vitamin D receptor (VDR) activation.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume132
Issue number1-2
DOIs
StatePublished - Oct 2012

Keywords

  • Calcitriol
  • Diabetes
  • Endothelial cells
  • Paricalcitol
  • Thioredoxin
  • Vitamin D

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