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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.
While Zinc deficiency is a common complication in chronic kidney disease, decreased serum zinc levels have also been reported in acute kidney injury. In particular, several studies have indicated alterations in zinc homeostasis in cisplatin nephrotoxicity, yet the detailed pathophysiology remains unclear. Therefore, this study aimed to investigate renal zinc homeostasis in cisplatin nephrotoxicity by focusing on the zinc transporters. Furthermore, as autophagy is reported to have a protective role in cisplatin nephrotoxicity, we also investigated the association between the changes in zinc homeostasis and the autophagy-lysosome pathway.
We used C57BL/6N wild-type mice and ZIP14 knockout (KO) mice on a C57BL/6 background. To evaluate cisplatin-induced nephrotoxicity, mice were sacrificed at 6 hours, 1 day, and 3 days after cisplatin administration. The expression of zinc transporters in renal tissue was quantified using real-time PCR. Additionally, renal tissue zinc concentration was assessed via fluorescent staining for free zinc with Zinpyr-1. A comprehensive proteomic analysis was conducted to evaluate changes in protein expression associated with cisplatin nephrotoxicity. For in vitro experiments, immortalized mouse proximal tubular epithelial cells and mouse embryonic fibroblasts were utilized. These cell lines were subjected to zinc loading and treatment with the zinc ionophore clioquinol to assess cellular responses.
Six hours after cisplatin administration, the expression of the ZIP family which is responsible for cellular zinc uptake was decreased. In contrast, at 1 and 3 days post-administration, their expression was increased, with a particularly marked upregulation of ZIP14. Consequently, cisplatin administration to ZIP14 KO mice resulted in exacerbated kidney injury compared to wild-type mice. Furthermore, a decrease in intracellular labile zinc was observed 3 days after cisplatin treatment, a reduction that was even more pronounced in the ZIP14 KO mice. Proteomic analysis revealed that proteins involved in the lysosomal pathway were downregulated in ZIP14 KO mice. This finding led us to focus on Transcription Factor EB (TFEB), the master regulator of lysosomal function. Since TFEB activity was decreased in conjunction with intracellular labile zinc deficiency, we evaluated the relationship between zinc and TFEB in vitro. TFEB was activated in a zinc-dependent manner. Furthermore, we demonstrated that zinc activates TFEB through the ATG conjugation system (composed of autophagy-related genes) in an autophagy-independent manner.
These findings suggest that ZIP14-mediated zinc influx confers protection against cisplatin nephrotoxicity by preventing the reduction of TFEB activity. However, as ZIP14 has also been reported to promote cancer-related muscle atrophy, its potential involvement in cisplatin-induced myopathy is a concern. Given this dual role of ZIP14 in both renal protection and the promotion of muscle atrophy, targeting the downstream TFEB pathway may represent a more favorable therapeutic strategy for managing cisplatin nephrotoxicity.
