title: Vitamin D3 Partly Antagonizes Advanced-Glycation Endproducts-Induced NFκB Activation in Mouse Podocytes.
abstract: OBJECTIVE
  We have previously shown that advanced glycation-endproducts (AGEs) induced NFκB activation in differentiated mouse podocytes. This NFκB activation may contribute to the progression of renal disease and mediation of fibrosis by various mechanisms. This study was undertaken to test whether this detrimental response may be reversed by vitamin D3 or its analogue paricalcitol.
  
  
  METHODS
  Differentiated mouse podocytes were challenged with glycated bovine serum albumin (AGE-BSA), or non-glycated control BSA (in the presence or absence of various concentrations of vitamin D3 (decostriol, 1α,25-dihydroxyvitamin D3)) or its active analog paricalcitol. Quantitative mRNA expressions were measured by real-time PCR, whereas protein expressions were determined by Western blotting followed by densitometry. Cytoplasmic and nuclear protein expression of the NFκB subunit p65 (Rel A) were determined by Western blotting. Furthermore, the ratio of phosphorylated to non-phosphorylated IκB-α was measured using specific antibodies. Electrophoretic mobility shift assays and a capture ELISA assay were used to assess NFκB transactivation in vitro. In addition, NFκB transactivation was also monitored in HEK-NFκBIA reporter cells using live cell luminometry.
  
  
  RESULTS
  Podocytes expressed the receptor for vitamin D. The vitamins did not suppress receptor for AGEs (RAGE) expression; instead, they rather upregulated RAGE. Although vitamin D3 and paricalcitol partly and differentially modified some of the studied parameters, both hormones inhibited AGE-BSA-induced NFκB transactivation, presumably by various mechanisms including the upregulation of IκB-α protein, keeping NFκB sequestered in an inactive state in the cytoplasm.
  
  
  CONCLUSIONS
  Vitamin D3 or its analog paricalcitol partly prevented AGE-mediated NFκB activation, an important feature of diabetic nephropathy (DN). Whether this in vitro finding is of clinical relevance to prevent/treat DN requires further studies.
authors: Department of Internal Medicine III, University Hospital Jena, Jena, Germany.
authors: Christiane
authors: C
authors: Rüster
authors: Sybille
authors: S
authors: Franke
authors: Stefanie
authors: S
authors: Reuter
authors: Ralf
authors: R
authors: Mrowka
authors: Tzvetanka
authors: T
authors: Bondeva
authors: Gunter
authors: G
authors: Wolf
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D002762:Cholecalciferol / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D002762:Cholecalciferol