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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.
IgA nephropathy (IgAN) is recognized as an immune complex–mediated glomerular disease; however, its underlying mechanisms remain unclear. We previously identified IgA autoantibodies targeting mesangial cell (MC) surface autoantigens, β2-spectrin and CBX3, both of which are generally recognized as ubiquitously expressed intracellular proteins, in patients with IgAN (Nihei Y. Sci Adv. 2023, Higashiyama M. Life Sci Alliance). In our previous work, Sparsentan (SP), a dual endothelin and angiotensin receptor antagonist (DEARA), significantly reduced proteinuria in gddY mice, a murine model of IgAN (Nagasawa H. Nephrol Dial Transplant. 2024). In this study, we investigated whether endothelin-1 (ET-1) and angiotensin II (Ang II) regulate the MC-surface expression of these autoantigens.
Selective surface expression of β2-spectrin and CBX3 on mesangial cells was confirmed by immunostaining of primary human mesangial cells (HMCs), human umbilical vein endothelial cells (HUVECs), and podocytes following fixation with 4% PFA.
To further confirm HMC-surface β2-spectrin and CBX3 expression, immunoelectron microscopy was performed. HMCs cultured for 48 hours were fixed, labeled with anti–β2-spectrin or anti-CBX3 antibodies followed by colloidal gold, and processed for transmission electron microscopy using standard fixation, dehydration, and embedding procedures.
To examine the effects of Ang II and ET-1 on mesangial IgA deposition in vivo, four-week-old gddY mice were treated with control chow (CC), SP for 12 weeks, or SP for 8 weeks followed by CC for 4 weeks (SP/CC) (n = 4 per group; one outlier was excluded from the SP group, and one mouse died in each of the other groups). Glomerular IgA deposition and serum IgA levels were evaluated.
To further investigate the effects of Ang II and ET-1 on HMC-surface autoantigen expression in vitro, HMCs were serum-starved and subsequently stimulated with Ang II, ET-1, or both under 0.5% BSA conditions. Cell-surface expression of β2-spectrin and CBX3 was assessed by immunofluorescence microscopy following fixation with 4% PFA.
In vitro, immunofluorescence staining revealed that surface expression of β2-spectrin and CBX3 was prominent on HMCs but rarely detected on HUVECs and podocytes. Immunoelectron microscopy confirmed β2-spectrin and CBX3 localization on the HMC surface, indicating selective expression on mesangial cells.
In vivo, SP treatment significantly reduced glomerular IgA deposition compared with CC (p = 0.043). In contrast, the SP/CC group exhibited a reversible exacerbation of IgA deposition (p = 0.072 vs. SP).
In vitro, stimulation of HMCs with Ang II and/or ET-1 increased surface expression of β2-spectrin (p = 0.0071, 0.0008, and 0.0091 for Ang II, ET-1, and both vs. control, respectively) and CBX3 (p = 0.97, 0.01, and 0.0001, respectively).
ET-1 and Ang II enhance the surface expression of β2-spectrin and CBX3 on HMCs, which may contribute to the reduction in mesangial IgA deposition observed with SP treatment in gddY mice. Further studies are warranted to elucidate the signaling pathways linking angiotensin and endothelin receptor activation to mesangial autoantigen exposure.
