Figure 6

ALK5 as a modulator of cystic growth in cell culture and expression of ALK4/5 in human ADPKD kidneys. Effects of SD208 (1 and 0.1 µM) after 10 days exposure on cyst area (a), proliferation (b) and apoptosis (c) in MDCKII cells compared to DMSO and forskolin controls. Results represented by median +/− IQR. Significance via Kruskal-Wallis test with Dunn’s multiple comparison, p values represented by * (****p ≤ 0.0001, ***p ≤ 0.001, **p ≤ 0.01, *p ≤ 0.05 and non-significant (ns): p > 0.05.). (di, ii, iii) Representative images of SD208 effects on cyst area, proliferation and apoptosis respectively compared to DMSO or forskolin. Podocalyxin/gp135 was used to define lumen formation with nuclear DAPI marker (di), Ki67 and cleaved caspase 3 antibodies used to measure proliferation and apoptosis respectively with phalloidin apical markers (dii and diii). Microarray expression profile of ALK5 (e) and ALK4 (f) in human kidney tissues derived from 5 polycystic kidney samples and 3 non-polycystic kidney samples. Polycystic sample tissues are separated into minimally cystic, small cysts (<1 ml), medium cysts (10–20 ml) and large cysts (>50 ml). Results represented by mean +/− SEM. Significance via one-way ANOVA with Dunnett’s multiple comparison, p values represented by * (****p ≤ 0.0001, ***p ≤ 0.001, **p ≤ 0.01, *p ≤ 0.05 and non-significant (ns): p > 0.05).