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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.
High mobility group protein B1 (HMGB1) is predominantly located in the nucleus, where it is involved in chromatin structure and transcription. On the other hand, under certain stress conditions, HMGB1 migrates to the cytoplasm and, further, to the extracellular space, acting as damage-associated molecular pattern (DAMP) molecule through receptors such as TLR4 and RAGE to induce inflammation. In previous studies, extracellular HMGB1 has been reported to exacerbate ischemia-reperfusion-induced acute kidney injury (AKI). However, there has been no prior research investigating the effects of deletion of Hmgb1 specifically in proximal tubular cells, which is most affected by AKI. Therefore, we examined its impact.
We generated mice in which proximal tubule-specific knockout of Hmgb1 can be induced in adulthood by using the Cre/loxP system. Specifically, Ndrg1CreERT2/+ mice, in which CreERT2 was inserted into the Ndrg1 gene locus expressed in the proximal tubules, were crossed with Hmgb1fl/fl mice. Ndrg1CreERT2/+;Hmgb1fl/fl (cKO) mice and their littermate controls (Ndrg1+/+;Hmgb1fl/fl, WT) were treated with tamoxifen (TAM) and used for experiments. As an in vivo model of ischemia-reperfusion-induced AKI, a unilateral ischemia-reperfusion model with contralateral nephrectomy was performed. For in vitro analysis, anoxic injury was evaluated using MCT cells, a proximal tubule-like cell line, transfected with Hmgb1 siRNA, and primary proximal tubular cells isolated from cKO mice. In addition, proximal tubules were separated from kidneys of cKO and WT mice without AKI induction, followed by microarray and Gene Ontology (GO) analyses.
We confirmed that proximal tubule-specific knockout of HMGB1 was achieved by immunofluorescence in cKO mice after TAM administration. We also confirmed that kidney histology and function were not changed by knockout of HMGB1 in the proximal tubule. Contrary to our expectations, in the AKI model, cKO mice showed significantly aggravated kidney histological injury and serum creatinine compared to controls, along with a significant increase in Lcn2 (NGAL) assessed by quantitative real-time PCR. Furthermore, cKO mice showed increased macrophage infiltration of the kidney tissue compared to WT mice. In vitro experiments also demonstrated that MCT cells transfected with Hmgb1 siRNA and primary cultured proximal tubular cells isolated from cKO kidneys exhibited exacerbated cell death under aoxic conditions compared to their control cells. In GO analysis comparing Hmgb1-deleted proximal tubules with non-deleted control ones, terms related to oxidative stress, cell cycle regulation, and inflammation ranked highly on the list.
Contrary to the expected outcome based on the role of extracellular HMGB1, proximal tubule–specific deletion of Hmgb1 exacerbated ischemia–reperfusion–induced AKI. In vitro models also consistently demonstrated that Hmgb1 deficiency aggravated cell death under anoxic conditions.
