We found that cystic cell-derived EVs/exosomes are able to induce the activation of recipient cells, including Pkd1 wild-type renal epithelial cells and fibroblasts, by downregulation of Pkd1 expression (Fig. 2a, b), and activation of PKD-associated signaling pathways (Fig. 2c) and fibrotic markers (Fig. 5e–h), leading to cyst formation and renal fibrosis (Figs. 4,, 5). Here, PKD1 is linked to cyst.