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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Nephronophthisis (NPH) is a genetic kidney disease characterized by progressive tubulointerstitial fibrosis. NPH has been clinically important as the most common cause of end-stage kidney disease in the juvenile period. Recent study revealed that NPH is not uncommon among adults with CKD. However, there is currently no reliable animal model that faithfully replicates the pathology of human NPH. Consequently, the molecular mechanism of NPH caused by NPHP1 deficiency, the most common form of NPH, has not yet been elucidated. Therefore, novel models to recapitulate the pathology of NPH are required. In this study, we used human induced pluripotent stem cells (iPSCs) to establish a 3D kidney organoid model of fibrosis that provides insight into the pathogenesis of NPH.
Wild-type iPSCs and NPHP1–/– iPSCs derived from the same cell line were differentiated into 3D kidney organoids, with subsequent analysis of phenotypes associated with NPHP1 deficiency. Initially, we compared the morphology of both wild-type and NPHP1–/– organoids by immunofluorescence. Subsequently, fibrosis was induced via IL-1β treatment, and differences in fibrosis severity between the two groups were evaluated. Finally, we applied compound candidates to evaluate their potential anti-fibrotic effects in organoids.
We successfully generated kidney organoids from both wild-type and NPHP1–/– iPSCs. In the absence of fibrosis stimulation, there were no observable differences in morphology, including nephron-like structures or fibrotic features, between the two groups. This is consistent with the clinical course of human NPH caused by NPHP1 deficiency, in which kidney dysfunction does not appear during the postnatal period. On the other hand, fibrosis was triggered by a significantly lower concentration of IL-1β in NPHP1–/– organoids compared to wild-type organoids. These results suggest that the NPHP1-deficient kidneys are more sensitive to fibrotic stimuli than the wild-type kidney, which may explain why NPHP1-deficient NPH patients reach end-stage kidney disease earlier. Lastly, we confirmed that NPHP1 binds to specific molecular components of the Hippo signaling pathway, which is known to promote fibrotic responses, and that administration of the Hippo signaling inhibitor Peptide-17 effectively suppressed IL-1β-induced fibrotic changes in NPHP1–/– organoids. These data indicate that the Hippo signaling pathway may contribute to the fibrotic changes observed in NPHP1-deficient NPH.
We established NPHP1-deficient 3D kidney organoids; the first human cell-based system capable of recapitulating NPH pathology. This model provides a valuable platform for elucidating disease mechanisms and advancing the development of therapeutic approaches for NPH. In fact, using this model, we extracted Hippo signaling inhibitors as potential therapeutic candidates for NPHP1-deficient NPH.
