Figure 1

Pioglitazone dose-dependently inhibits cyst swelling in a non-toxic manner. (a) Representative images of 3D-cultured mIMCD3-Pkd1^−/− cysts (cytoskeleton, F-actin) exposed with vehicle control (unstimulated, 0.2% DMSO), forskolin (stimulated, 2.5 µM) or forskolin (2.5 µM) plus increasing concentrations of pioglitazone. These max z-projections of a complete well were taken with the ImageXpress Micro XLS imager and are shown for presentation purposes. (b) With co-exposure to forskolin, pioglitazone dose-dependently reduces cyst swelling in mIMCD3-Pkd1^−/− cysts. At the highest concentrations (10 and 100 µM), cyst size is lower than unstimulated vehicle control (0.2% DMSO). Cyst size is normalised based on unstimulated vehicle control (0.2% DMSO, set at 0%) and stimulated control (2.5 µM forskolin, set at 100%). (c) Multiparametric phenotypic measurements indicate that compared to the toxic control staurosporine, pioglitazone does not induce inhibition of cyst swelling through cytotoxicity up to 1 μM. Toxic phenotype is normalised based on unstimulated control (0.2% DMSO, set at 0%) and toxic control (0.25 μM staurosporine, set at 100%). Each dot represents a replicate per condition (n = 4). FSK: forskolin, Stau: staurosporine.