Role of vitamin D in maintaining renal epithelial barrier function in uremic conditions

Milos Mihajlovic, Michele Fedecostante, Miriam J. Oost, Sonja K.P. Steenhuis, Eef G.W.M. Lentjes, Inge Maitimu-Smeele, Manoe J. Janssen, Luuk B. Hilbrands, Rosalinde Masereeuw*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

As current kidney replacement therapies are not efficient enough for end-stage renal disease (ESRD) treatment, a bioartificial kidney (BAK) device, based on conditionally immortalized human proximal tubule epithelial cells (ciPTEC), could represent an attractive solution. The active transport activity of such a system was recently demonstrated. In addition, endocrine functions of the cells, such as vitamin D activation, are relevant. The organic anion transporter 1 (OAT-1) overexpressing ciPTEC line presented 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and vitamin D receptor (VDR), responsible for vitamin D activation, degradation and function, respectively. The ability to produce and secrete 1α,25-dihydroxy-vitamin D3, was shown after incubation with the precursor, 25-hydroxy-vitamin D3. The beneficial effect of vitamin D on cell function and behavior in uremic conditions was studied in the presence of an anionic uremic toxins mixture. Vitamin D could restore cell viability, and inflammatory and oxidative status, as shown by cell metabolic activity, interleukin-6 (IL-6) levels and reactive oxygen species (ROS) production, respectively. Finally, vitamin D restored transepithelial barrier function, as evidenced by decreased inulin-FITC leakage in biofunctionalized hollow fiber membranes (HFM) carrying ciPTEC-OAT1. In conclusion, the protective effects of vitamin D in uremic conditions and proven ciPTEC-OAT1 endocrine function encourage the use of these cells for BAK application.

Original languageEnglish
Article number2531
JournalInternational journal of molecular sciences
Volume18
Issue number12
DOIs
Publication statusPublished - 26 Nov 2017

Keywords

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism
  • Cell Line
  • Cell Survival
  • Cytoprotection
  • Epithelial Cells/drug effects
  • Humans
  • Interleukin-6/metabolism
  • Kidney Tubules, Proximal/cytology
  • Organic Anion Transport Protein 1/metabolism
  • Oxidative Stress
  • Receptors, Calcitriol/metabolism
  • Toxins, Biological/toxicity
  • Vitamin D/pharmacology
  • Vitamin D3 24-Hydroxylase/metabolism
  • Vitamins/pharmacology

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