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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.
Bisphenol A (BPA), a pervasive environmental contaminant found in microplastics, is associated with the progression of chronic kidney disease (CKD), though its underlying mechanisms remain incompletely understood. Our preliminary metabolomics data revealed significant accumulation of BPA in CKD patients. We have previously demonstrated that SIRT2 acts as a negative regulator of renal fibrosis by deacetylating SMAD3. This study aims to investigate a novel mechanism through which BPA exacerbates renal fibrosis by inhibiting SIRT2, potentially via direct binding and an indirect TLR2-mediated NAD+ depletion pathway.
In vivo, C57BL/6J mouse models were treated with BPA, SIRT2 inhibitor (AGK7), or an agonist. Renal fibrosis was assessed through histological staining (Masson’s trichrome, PAS) and evaluation of fibrotic markers (CTGF, FN1). In vitro, human renal tubular epithelial (HK2) cells were treated with BPA, and SIRT2 was knocked down or overexpressed using adenoviruses.SMAD3 phosphorylation, nuclear translocation, and TGF-β signaling were analyzed by Western blot and immunofluorescence. The interaction between BPA and SIRT2 was predicted by molecular docking. TLR2 activation, PARP activity, and NAD+/NADH levels were measured.
BPA exposure significantly aggravated renal fibrosis in mice, accompanied by reduced SIRT2 expression and enhanced SMAD3 activation. Molecular docking revealed stable binding between BPA and SIRT2, primarily through Pi-Pi and alkyl interactions. In vitro, BPA treatment inhibited SIRT2 expression, promoted SMAD3 phosphorylation and nuclear translocation, and up-regulated TGF-β target genes—effects that were rescued by SIRT2 overexpression. Notably, BPA treatment activated TLR2 signaling, which in turn triggered the activation of poly(ADP-ribose) polymerases (PARPs), precipitating a severe depletion of intracellular NAD+ levels, the essential cofactor for SIRT2 activity. The fibrotic response to BPA was abrogated by TLR2 knockout, PARP inhibition, or NAD+ precursor supplementation in C57BL/6J mice.
Our findings demonstrate that BPA exacerbates renal fibrosis in C57BL/6J mice through a dual mechanism: 1) direct binding to and inhibition of SIRT2, and 2) indirect suppression of SIRT2 activity via a TLR2-driven PARP activation and subsequent NAD+ depletion axis. This disruption amplifies TGF-β/SMAD3 signaling. SIRT2 agonists, PARP inhibitors, and NAD+ precursors emerge as promising therapeutic strategies to mitigate BPA-induced nephrotoxicity.
