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dc.contributor.authorVormann, Marianne K.
dc.contributor.authorGijzen, Linda
dc.contributor.authorHutter, Simon
dc.contributor.authorBoot, Lisette
dc.contributor.authorNicolas, Arnaud
dc.contributor.authorvan den Heuvel, Angelique
dc.contributor.authorVriend, Jelle
dc.contributor.authorNg, Chee Ping
dc.contributor.authorNieskens, Tom T.G.
dc.contributor.authorvan Duinen, Vincent
dc.contributor.authorde Wagenaar, Bjorn
dc.contributor.authorMasereeuw, Rosalinde
dc.contributor.authorSuter-Dick, Laura
dc.contributor.authorTrietsch, Sebastian J.
dc.contributor.authorWilmer, Martijn
dc.contributor.authorJoore, Jos
dc.contributor.authorVulto, Paul
dc.contributor.authorLanz, Henriette
dc.date.accessioned2018-12-13T09:52:22Z
dc.date.available2018-12-13T09:52:22Z
dc.date.issued2018-08
dc.identifier.doihttps://doi.org/10.1208/s12248-018-0248-z
dc.identifier.urihttp://hdl.handle.net/11654/26951
dc.description.abstractProximal tubules in the kidney play a crucial role in reabsorbing and eliminating substrates from the body into the urine, leading to high local concentrations of xenobiotics. This makes the proximal tubule a major target for drug toxicity that needs to be evaluated during the drug development process. Here, we describe an advanced in vitro model consisting of fully polarized renal proximal tubular epithelial cells cultured in a microfluidic system. Up to 40 leak-tight tubules were cultured on this platform that provides access to the basolateral as well as the apical side of the epithelial cells. Exposure to the nephrotoxicant cisplatin caused a dose-dependent disruption of the epithelial barrier, a decrease in viability, an increase in effluent LDH activity, and changes in expression of tight-junction marker zona-occludence 1, actin, and DNA-damage marker H2A.X, as detected by immunostaining. Activity and inhibition of the efflux pumps P-glycoprotein (P-gp) and multidrug resistance protein (MRP) were demonstrated using fluorescence-based transporter assays. In addition, the transepithelial transport function from the basolateral to the apical side of the proximal tubule was studied. The apparent permeability of the fluorescent P-gp substrate rhodamine 123 was decreased by 35% by co-incubation with cyclosporin A. Furthermore, the activity of the glucose transporter SGLT2 was demonstrated using the fluorescent glucose analog 6-NBDG which was sensitive to inhibition by phlorizin. Our results demonstrate that we developed a functional 3D perfused proximal tubule model with advanced renal epithelial characteristics that can be used for drug screening studies.
dc.description.urihttps://link.springer.com/article/10.1208%2Fs12248-018-0248-z
dc.language.isoen
dc.relation.ispartofThe APPS Journal
dc.accessRightsAnonymous
dc.subjectkidney-on-a-chip
dc.subjectnephrotoxiciy
dc.subjectapparent permeability (Papp)
dc.subjectProximal tubule
dc.subjecttransepithelial transport
dc.titleNephrotoxicity and Kidney Transport Assessment on 3D Perfused Proximal Tubules
dc.type01 - Zeitschriftenartikel, Journalartikel oder Magazin
dc.volume20
dc.issue5
dc.audienceScience
fhnw.publicationStatePublished
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publication
fhnw.InventedHereYes
fhnw.PublishedSwitzerlandNo
fhnw.pagination90
fhnw.IsStudentsWorkno
fhnw.publicationOnlineJa


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