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.
Highlights
It has been reported that chronic kidney disease (CKD), defined as the sustained presence of a decreased glomerular filtration rate (GFR) with or without increased albumin excretion, has a rather high global prevalence, estimated to be between 11% and 13% [1]
We demonstrated the ability of conditionally immortalized human proximal tubule epithelial cells (ciPTEC)-organic anion transporter 1 (OAT1) to produce the most active form of vitamin D, 1,25(OH)2D3, and its beneficial effect on various aspects of uremic conditions in ciPTEC-OAT1, including the protective effect on epithelial monolayer tightness
Considering the importance of the vitamin D deficiency often observed in CKD and end-stage renal disease (ESRD), and the fact that vitamin D production is one of the main endocrine functions of proximal tubule cells, we were interested in determining whether ciPTEC-OAT1, intended for bioartificial kidney (BAK) purposes, possess all the necessary enzymes responsible for vitamin D metabolism
Summary
It has been reported that chronic kidney disease (CKD), defined as the sustained presence of a decreased glomerular filtration rate (GFR) with or without increased albumin excretion, has a rather high global prevalence, estimated to be between 11% and 13% [1]. A unique cell type created by our group is represented by urine-derived conditionally immortalized PTEC (ciPTEC) [27,28] equipped with the organic anion transporter 1 (OAT1) [29] This transport protein is responsible for the uptake of many anionic waste products in kidney proximal tubule, as a first step in their renal excretion. We focused on the beneficial effects of vitamin D on cell viability, oxidative stress, inflammation and epithelial monolayer barrier function of ciPTEC-OAT1 cultured on biofunctionalized polyethersulfone HFM. In order to aasssseesss tthhee ssttaabbiilliittyy ooffcciiPPTTEECC--OOAAT1 monolayer in uremic conditions and the effect of vitamin DDononitsitsightitgnhetsns,ecsse,llscewllesrewcuerleturceudltounreLd-3,o4n-dLih-3y,d4r-odxihyypdhreonxyylaplhaneninyela(lLa-nDiOnePA(L)a-DndOcPoAll)aagnedn cIVollcaogaetnedIVHcFoMat,eads HdeFsMcr,ibaesddpesrcerviiboeudslpyr[e3v0i,o3u2s]l.yT[i3g0h,t32m].oTnioglhatyemr ownaoslacyoenrfiwrmasedcobnyfirthmeedprbesyenthce presence of zonula occludens 1 (ZO-1) tight junction protein and actin staining (Figure 6a). Figeuxraem6icneddepcoicntdsiatiosnchs.ematic presentation of inulin-FITC leakage in HFM carrying ciPTEC-OAT1 in examined conditions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
