Fig. 1: Cyst formation by Polycystin-1-deficient cells depends on cAMP- and Ca²⁺-activated Cl⁻ secretion.

a, b Wild type (Pkd1^+/+) and polycystin-1-deficient (Pkd1^−/−) principal-like MDCK cells (clones #1) were cultured in a collagen matrix in the absence (−FSK) or presence (−FSK) of 10 µM forskolin. Forskolin induced cyst formation by PKD1^+/+ cells within 5 days (^§P < 0.0001). Pkd1^−/− cells demonstrated cyst formation even in the absence of FSK (^#P < 0.0001) and formed larger cysts in the presence of FSK (^#P < 0.0001) (n = 105 cysts examined in n = 3 independent experiments). c Deletion of Polycystin-1 in Pkd1^−/− cells induced an increase in basal intracellular cAMP concentrations (−FSK, ^#P = 0.041). FSK-stimulation further enhanced cAMP levels in both Pkd1^+/+ and Pkd1^−/− cells (^§P = 0.0008) (each n = 3 independent experiments). cAMP levels in Pkd1^+/+ cells were set to 100%). d, e Cyst growth was strongly inhibited in both Pkd1^+/+ and Pkd1^−/− cells by CFTRinh172 (CFTRinh; 10 µM, ^§P < 0.0001), niclosamide (Niclo; 1 µM, ^§P = 0.0001), and suramin (Sur; 100 µM, ^§P = 0.002), but was further augmented by ATP (10 µM, ^§P = 0.002). Bars 200 μm (n = 87 cysts examined in n = 3 independent experiments). Mean and error bars indicating ±SEM. ^#Unpaired two-sided t test comparing Pkd1^+/+ with Pkd1^−/−, ^§unpaired two-sided t test comparing effects by forskolin, ATP or inhibitors. Source data are provided as a Source Data file.