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Article

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.
Int. J. Mol. Sci. 2017, 18(12), 2531; https://doi.org/10.3390/ijms18122531
Received: 29 September 2017 / Revised: 28 October 2017 / Accepted: 22 November 2017 / Published: 26 November 2017
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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MDPI and ACS Style

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. https://doi.org/10.3390/ijms18122531

AMA Style

Mihajlovic M, Fedecostante M, Oost MJ, Steenhuis SKP, Lentjes EGWM, Maitimu-Smeele I, Janssen MJ, Hilbrands LB, Masereeuw R. Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions. International Journal of Molecular Sciences. 2017; 18(12):2531. https://doi.org/10.3390/ijms18122531

Chicago/Turabian Style

Mihajlovic, Milos, Michele Fedecostante, Miriam J. Oost, Sonja K.P. Steenhuis, Eef G.W.M. Lentjes, Inge Maitimu-Smeele, Manoe J. Janssen, Luuk B. Hilbrands, and Rosalinde Masereeuw. 2017. "Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions" International Journal of Molecular Sciences 18, no. 12: 2531. https://doi.org/10.3390/ijms18122531

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