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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.
Acute kidney injury (AKI) is a major precipitant of chronic kidney disease (CKD), yet effective interventions remain limited. Maladaptively repaired renal tubular epithelial cells (TECs) after AKI commonly undergo cell-cycle arrest and acquire a pro-inflammatory senescence-associated secretory phenotype (SASP). Targeting cellular senescence and the SASP has therefore emerged as a promising strategy to prevent AKI–CKD transition. ZAK, a MAP3K family member, has been implicated in DNA-damage responses and inflammatory cytokine regulation. This study sought to define the role of ZAK in TEC senescence and to evaluate the therapeutic potential of pharmacological ZAK inhibition in mitigating the transition from AKI to CKD.
Murine AKI–CKD models were established using ischemia–reperfusion injury (IRI) and folic acid (FA) nephropathy to assess ZAK expression and localization in the kidney. Small-molecule inhibition of ZAK was used to determine effects on renal function, interstitial fibrosis, and cellular senescence. Mechanistic studies included overexpression of a constitutively active ZAK in primary TECs to evaluate senescence markers. In an oxidative stress–induced senescence model, ZAK was silenced or inhibited to examine changes in senescence and SASP . ZAK-interacting proteins were identified by co-immunoprecipitation coupled with mass spectrometry, and the impact of ZAK on STING protein stability was interrogated.
In the IRI model, ZAK mRNA and protein were significantly upregulated and localized predominantly to TECs. Pharmacological ZAK inhibition improved renal function, attenuated fibrosis, and reduced senescence markers (p16, p21, and SA-β-gal) in both IRI and FA models. In vitro, constitutively active ZAK elicited a senescent phenotype in TECs, whereas ZAK knockdown or kinase inhibition mitigated H₂O₂-induced senescence and the SASP. Mechanistically, activation of the cGAS–STING pathway enhanced ZAK synthesis; reciprocally, ZAK promoted the association of the deubiquitinase USP20 with STING, thereby limiting ubiquitination-mediated STING degradation.
After AKI, ZAK is induced in renal tubular epithelial cells, where it drives cellular senescence and SASP production, thereby propagating AKI–CKD progression. Mechanistically, ZAK constrains STING ubiquitination and degradation, establishing a ZAK–STING–NF-κB positive feedback loop. These findings identify ZAK as a tractable therapeutic target to interrupt the transition from AKI to CKD.
