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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.
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Abstract titles should be brief and reflect the content of the abstract.
We reported that renal tubule (RT) angiotensinogen (Agt) gene deletion attenuates glomerular hyperfiltration, tubular injury, SGLT2 expression in renal proximal tubules (RPTs) and decreases urinary albumin-creatinine ratio (uACR) of T1D Akita mice (Diabetes 2025). The present study was aimed to explore the molecular mechanisms underlying tubulopathy in diabetes.
Male non-diabetic control, RT-Agt knockout (KO), Akita, and Akita RT-Agt KO mice at 42 weeks old, HK-2 (human immortalized proximal tubule cell line) and MDCK (Madin-Darby Canine Kidney) cells were studied. Tubular cell size, luminal area, interstitial fibrosis, apoptosis, mitochondrial oxidative stress and function, senescence (senescence-associated β-galactosidase (SA β-Gal)) and senescence-associated secretory phenotype (SASP) were assessed.
Akita mice exhibited significant increases in tubular cell size, luminal area, renal dihydroethidium (DHE) and 8-Hydroxy-2’-deoxyguanosine (8-OHdG) staining, uACR, apoptosis, expression of NADPH Oxidase 4 (NOX4), transforming growth factor-beta 1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1) and fibronectin, disruption of mitochondrial cristae (electronic microscopy analysis), SA β-Gal activity, SASP gene (Ccl2, Cxcl1 and Tnf-α) expression, and immunofluorescent staining of p16 in distal tubules. These abnormalities were markedly attenuated in Akita RT-Agt- KO mice. Culture of HK2 cells with high glucose (HG) (35 mM D-glucose) and Ang II (10-7 M) triggered NOX4-mediated mitochondrial oxidative stress (MitoSox staining), reduced mitochondrial transmembrane potential (JC1 staining), disrupted mitochondrial morphology (Mitotracker assay), increased p16 expression, SA β-Gal activity and SASP gene expression in HK-2 cells. These changes were attenuated by losartan (an AT1R blocker) or apocynin (an NOX4 inhibitor). Furthermore, addition of Ang II/HG-induced senescent MDCK-derived conditioned medium to HK-2 cells facilitated the epithelial-to-mesenchymal transition in HK2 cells, which was reversed by losartan or apocynin treatment.
Deletion of Agt in RT attenuates tubulopathy, at least in part, through lessening ROS-mediated DNA damage, mitochondrial dysfunction and senescence in Akita mice. Parts of the data, will be presented at the Annual Meeting of the American Society of Nephrology, Houston, TX, USA, November 5-9, 2025.
