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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.
Kidney fibrosis represents a self-perpetuating injury pathway that is activated in nearly all forms of chronic kidney disease (CKD) leading to end-stage renal disease (ESRD), yet no renal antifibrotic therapy has been developed to date. NUAK1, a member of the AMP-related kinase family, is upregulated in fibrotic tissues and correlated with progressive dysfunction in human transplant kidneys. Mechanistically, NUAK1 activates YAP/TAZ transcriptional activity by destabilizing a Hippo pathway kinase LATS1. Moreover, NUAK1 expression itself is driven by YAP/TAZ, establishing a profibrotic positive feedback loop that sustains fibrosis. Therefore, we hypothesized that inhibition of NUAK1 could be a novel antifibrotic approach to deterring the progression of CKD. Toward that end, we have developed a series of potent, selective, and bioavailable NUAK1 inhibitors to test the hypothesis.
NRK-49F rat renal fibroblasts were treated with TGF-β, and expression of NUAK1, YAP-targeted genes, and profibrotic gene were evaluated by qRT-PCR and western blotting. Alpha-smooth muscle actin (α-SMA) expression and YAP nuclear translocation were measured using immunocytochemistry. NUAK1 inhibitors were identified and developed through in-house kinase library screening followed by iterative optimization for potency, selectivity, and ADME properties. Lead compounds were further characterized in cells by NanoBRET as well as a high-content screening for α-SMA. For in vivo proof-of-concept validation, renal fibrosis was induced using a unilateral ureteral obstruction (UUO) mouse model.
TGF-β stimulation of NRK-49F cells induced fibrotic activation. NUAK1 expression was increased along with profibrotic marker, such as α-SMA, at both mRNA and protein levels. Also, YAP activity was enhanced, as evidenced by its nuclear translocation and the upregulation of its downstream target gene, CCN2. In the TGF-β -stimulated cells, inhibition of NUAK1, either pharmacologically or genetically, suppressed YAP nuclear localization and decreased the expression of CCN2 and α-SMA. In a human renal cell–fibroblast co-culture system, NUAK1 inhibition attenuated TGF-β–induced α-SMA and the pro-inflammatory cytokines sIL-6 and sIL-8. In the UUO-induced renal fibrosis model, administration of a NUAK1 inhibitor significantly reduced renal fibrotic lesions, extracellular matrix deposition, and expression of profibrotic markers.
Our findings demonstrate that NUAK1 plays a critical role in renal fibrogenesis through regulation of YAP activity and its downstream profibrotic signaling. Targeting NUAK1 effectively disrupted the profibrotic feedback loop mediated by YAP/TAZ, suggesting that inhibition of NUAK1 can reprogram fibroblast activation and limit fibrogenic signaling. Collectively, these findings highlight NUAK1 inhibitors as promising renal antifibrotic candidates with potential translational relevance for CKD.
