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Int. J. Mol. Sci. 2017, 18(12), 2531; https://doi.org/10.3390/ijms18122531

Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions

1
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands
2
Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands
3
Department of Nephrology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
*
Author to whom correspondence should be addressed.
Received: 29 September 2017 / Revised: 28 October 2017 / Accepted: 22 November 2017 / Published: 26 November 2017
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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. View Full-Text
Keywords: bioartificial kidney; conditionally immortalized proximal tubule cells; chronic kidney disease; end-stage renal disease; vitamin D; uremic toxins; epithelial barrier bioartificial kidney; conditionally immortalized proximal tubule cells; chronic kidney disease; end-stage renal disease; vitamin D; uremic toxins; epithelial barrier
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Mihajlovic, M.; Fedecostante, M.; Oost, M.J.; Steenhuis, S.K.P.; Lentjes, E.G.W.M.; Maitimu-Smeele, I.; Janssen, M.J.; Hilbrands, L.B.; Masereeuw, R. Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions. Int. J. Mol. Sci. 2017, 18, 2531.

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