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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.
Sustained expression of KIM-1 is recognized as being nephrotoxic. Our group previously reported TW-37 as an inhibitor targeting KIM-1-mediated endocytosis. Subsequently, we discovered that the KIM-1-dependent endocytosis of palmitate-bound albumin triggers activation of the NLRP3 inflammasome, elicits a DNA damage response, induces cell cycle arrest, promotes cellular senescence, and results in the production of pro-inflammatory and pro-fibrotic cytokines. TW-37 is also known as a senolytic agent, as it induces cell death in senescent cells. The present study aimed to examine the comparatively long-term impact of TW-37 on primary human renal proximal tubular epithelial cells (hRPTECs) in culture.
Primary hRPTECs were established from the non-malignant portions of kidneys resected from patients with malignancy, after receiving written informed consent (Approved by the Ethics Review Committee of Tokyo Medical and Dental University School of Medicine: M2022-005). The tissue was cultured in a serum-free medium supplemented with epidermal growth factor. These established cells were seeded onto 6-well plates at a density of 6×10^5 cells/well on Day 0. On Day 2, the medium was replaced with 10% FBS-DMEM containing either TW-37 or DMSO (as a control). Cells were cultured for 8 days (Day 2 to Day 10), during which the medium containing TW-37 or DMSO was periodically replaced. The expression levels of KIM-1, NF-κB, IL-1β, p16, caspase-3, and PD-L1 were assessed by Western blotting. Immunofluorescence staining was employed to evaluate Megalin expression.
Treatment with TW-37 resulted in reduced KIM-1 expression. A similar reduction was observed for NF-κB and IL-1β, suggesting a potential inhibition of the NF-κB-NLRP3-IL-1β pathway. Although p16 was present in the control cells, TW-37 administration downregulated p16 expression without elevating caspase-3 levels. This finding indicates that TW-37 might possess anti-senescence properties that are independent of apoptosis. Additionally, TW-37 reduced the expression of PD-L1. Megalin expression remained unaltered by the TW-37 treatment, implying that the cells retained their differentiated phenotype.
These findings suggest that over a longer duration, TW-37, by inhibiting KIM-1, may trigger intracellular anti-inflammatory and anti-senescence mechanisms, potentially conferring a renoprotective benefit.
