Fig. 3
From: Proximal tubule-on-chip as a model for predicting cation transport and drug transporter dynamics
Metformin and creatinine treatments alter drug transporter transcriptional expression and endogenous metabolite production. Fold changes regarding the relative expression levels of mRNA transporter expressions of RPTEC/TERT1 cell line in dual-channel device under treatment of (A) metformin (Met, 100 µM, N = 3), in presence or not of cimetidine (C, 100 µM, N = 3) and (B) creatinine (Creat, 10 µM, N = 3) in presence or not of ritonavir (R, 15 µM, N = 3) or cimetidine (C, 100 µM, N = 3). Error bars represent standard deviations. Statistical significance was determined using Kruskal Wallis test, asterisks (*) indicate statistically significant differences with respect to untreated PT-on-chip (N = 5, *p-value < 0.05, **p-value < 0.01, ***p-value < 0.001). (C) Heat map of intracellular metabolites altered under metformin (left panel) and creatinine (right panel) treatment. Data were standardized by auto scaling and hierarchically clustered with Ward method and represented by mean of 3 independent replicates. Metabolomic clustering was achieved using the MetaboAnalyst 6.0 Statistical Analysis online tool. (D) Venn diagram of shared up regulated and down regulated metabolite under treatment including the top 5 most up and down regulated for each treatment separately.
