Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions
AbstractAs 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
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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.
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.Chicago/Turabian Style
Mihajlovic, Milos; Fedecostante, Michele; Oost, Miriam J.; Steenhuis, Sonja K.P.; Lentjes, Eef G.W.M.; Maitimu-Smeele, Inge; Janssen, Manoe J.; Hilbrands, Luuk B.; Masereeuw, Rosalinde. 2017. "Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions." Int. J. Mol. Sci. 18, no. 12: 2531.
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