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. 2022 Sep 21;8(38):eabq0866. doi: 10.1126/sciadv.abq0866

Fig. 3. Identification of novel therapeutic targets for ARPKD and drug screening tests using commercially available compounds.

Fig. 3.

(A) Schematic illustrating the strategy to identify flow-specific pathways and common pathways by comparing PKHD1−/− versus PKHD1+/− organoids with flow, forskolin (FK) treatment, or static culture. The number of pathways is shown with parenthesis. (B) Proportions of pathways categorized in the three-level iterative analysis. (C) Schematic of the strategy to identify novel therapeutic targets for ARPKD. (D) Immunocytochemistry for proximal tubule (LTL), distal tubule (CDH1), and podocyte (PODXL) in PKHD1+/− organoids under flow and PKHD1−/− organoids treated with and without candidate compounds (T-5224, NSC23766, 2-MeOE2, Z-DEVD-FMK, quercetagetin, and rhCXCL16) under flow on day 35. Scale bars, 50 μm. (E) Distal tubular diameter in PKHD1+/− organoids under flow and PKHD1−/− organoids treated with and without each compound under flow on day 35. (F) DiVenn diagram that compares pathways in our ARPKD model and human ADPKD dataset. Values represent means ± SD. ***P < 0.001, ****P < 0.0001.