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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.
We previously demonstrated that the transcription factor ATOH8 suppresses TGF-β signaling in podocytes and protects against glomerulosclerosis (ASN 2025). However, the downstream mechanisms of ATOH8 loss and its regulatory factors remain unclear. In this study, we further investigated how ATOH8 expression is regulated and how its loss contributes to podocyte injury and glomerular disease.
ATOH8 localization in mouse kidneys was examined by immunohistochemistry, immunofluorescence, and in situ hybridization. In vitro, human podocytes were transduced with shRNA targeting ATOH8 (ATOH8sh). Transcriptomic profiling by RNA sequencing, evaluation of TGF-β/SMAD signaling activity using reporter assays, and apoptosis analysis were performed to assess functional consequences. The potential epigenetic regulation of ATOH8 expression and localization was examined using the EZH2 inhibitor GSK126. In vivo relevance was analyzed in adriamycin (ADR)-induced focal segmental glomerulosclerosis (FSGS) models in wild-type and Atoh8-deficient mice. ATOH8 expression was also examined in rat, mouse, and human kidneys with glomerular disease.
Consistent with our previous findings, ATOH8 was localized in a subset of podocytes and was markedly downregulated by TGF-β stimulation. This suppression was abolished by cycloheximide, indicating dependence on de novo protein synthesis. Knockdown of ATOH8 in podocytes upregulated extracellular matrix–related genes including COL1A1, SNAI1, and VIM, and activated TGF-β/SMAD signaling, as evidenced by nuclear accumulation of SMAD2/3 and a 2.4-fold increase in SMAD reporter activity even without exogenous TGF-β stimulation (p = 0.0044). Functionally, ATOH8 knockdown reduced cell viability and increased apoptosis. Treatment with the EZH2 inhibitor GSK126 enhanced ATOH8 expression and promoted its nuclear localization, suggesting epigenetic regulation.
In vivo, Atoh8-deficient mice exhibited no overt renal abnormalities at baseline, but following ADR-induced injury, they developed significantly more severe glomerulosclerosis compared with wild-type mice (17.9% vs 4.8%, p = 0.00005). These mice also showed increased renal cortical Tgfb1 and Col4a1 mRNA expression despite similar albuminuria levels. In human kidney biopsies, ATOH8 expression was reduced by approximately 60–76% in IgA nephropathy, diabetic kidney disease, membranous nephropathy, ANCA-associated vasculitis, and lupus nephritis, while it was relatively preserved in minimal change disease.
This study extends our previous report by demonstrating the mechanism through which TGF-β suppresses ATOH8 expression via de novo protein synthesis and by demonstrating that ATOH8 loss not only activates TGF-β signaling but also induces podocyte susceptibility to apoptosis and injury. Furthermore, the regulation of ATOH8 by the histone methyltransferase EZH2 suggests an epigenetic mechanism underlying its suppression. Together, these findings identify ATOH8 as a critical protective factor maintaining podocyte integrity and a potential therapeutic target for limiting glomerular injury.
