Figure 2

Omarigliptin treatment reduces cyst formation in a zebrafish nephronophthisis model and expression analysis of target pathway components. (a) Representative brightfield images of wild-type zebrafish embryos at 48 hpf, following 24-h treatment with either DMSO (vehicle control) or Omarigliptin (25 µM), indicating no developmental toxicity. Bar = 500 µm. (b) Quantification demonstrating the absence of cyst-inducing effects in wild-type embryos treated with DMSO or 25 µM Omarigliptin. (c) The dose-response analysis reveals a concentration-dependent reduction in glomerular cysts in nphp1/nphp4 double morphant embryos treated with increasing concentrations of Omarigliptin (2.5–25 µM). Statistical comparison between DMSO and 25 µM Omarigliptin treatment shows a significant reduction in cyst formation (p = 0.0186). OM, Omarigliptin. (d) Whole-mount in situ hybridization showing the temporal and spatial expression patterns of dpp4, gcgra, and gcgrb at the 16-somite stage, 1 dpf, and 2 dpf. Bar = 500 µm. (e–g) RT-PCR analysis showing the developmental expression profiles of dpp4 (e), gcgra (f), and gcgrb (g) from the 16-somite stage to 3 dpf, with ef1a serving as the loading control. Data are presented as mean ± SEM. Each circle represents an independent experiment. The total number of embryos analyzed per condition (n) is indicated below each graph.