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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.
Disruption of the slit diaphragm (SD) contributes to podocytopathy and proteinuria in diabetic kidney disease (DKD). We analyzed public datasets associated with tight, adhesion, gap junctions and detected AXL as a novel factor in the SD region. This study aims to investigate the mechanism of AXL on ZO-1, a key SD junctional protein, in podocyte injury in DKD.
The level of AXL in renal tissues of DKD patients and diabetic mice was examined through database mining, single-cell sequencing, and molecular biological techniques. Immunoelectron microscopy, immunofluorescence, and RNAscope were applied to determine the localization of AXL in renal tissues. Mass spectrometry, Co-IP, and BLI were used to screen potential target molecules of AXL. FRAP was employed to assess the regulatory effect of AXL on ZO-1 phase separation. Podocyte-specific AXL knockout mice were established to validate the role of AXL on DKD phenotypes and its functional impact.
Public datasets mining linked AXL to cell adhesion and tight junction processes in podocytes. AXL was expressed in podocytes and localized at the SD region. The level of AXL in renal tissues of DKD patients increased with advancing pathological stages, and predicted increased proteinuria and worsened renal function. In vivo animal experiments demonstrated AXL overexpression induced podocyte injury and exacerbated proteinuria and disease progression in db/db mice, whereas the AXL inhibitor R428 significantly ameliorated these effects. Further, podocyte-specific knockout of AXL in STZ-induced diabetic mice alleviated renal injury and proteinuria. Mass spectrometry analysis revealed a significant enrichment of pathways associated with the tight junction protein ZO-1. RNAscope and immunofluorescence assays demonstrated co-localization of AXL and ZO-1. In normal human podocytes cultured in vitro, the expression of ZO-1 was arranged in a bead-like pattern along the cell membrane, and a reticular connection structure was formed between two cells. AXL knockdown, however, restored the disrupted membrane localization of ZO-1 induced by high glucose. Notably, in STZ mice in vivo, AXL overexpression disrupted the membrane localization of ZO-1. ZO-1 exhibits spontaneous phase separation, whereas AXL lacks this ability. The intracellular kinase domain of AXL binds to the PSG domain of ZO-1 and disrupted its phase separation.
Our findings demonstrate that under physiological conditions, AXL binds to ZO-1 to maintainthe homeostasis of ZO-1 phase separation and its membrane localization. In DKD, the upregulation of AXL disrupts ZO-1 phase separation and membrane localization, causes the loosening of tight junctions, thereby disrupting the SD integrity and exacerbating podocyte injury and proteinuria.
