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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.
The retinoic acid (RA) signaling pathway plays a complex dual role in maintaining renal homeostasis, providing protection during tissue repair and promoting disease progression when abnormally activated. Cadmium (Cd), a heavy metal, is an important environmental risk factor for chronic kidney disease (CKD). The mechanism of its toxicity to the kidneys, especially its impact on glomerular podocytes, has not been fully elucidated. Although research in the field of kidney transplantation suggests that RA metabolites have anti-rejection and anti-fibrotic potential, how Cd exposure interferes with the local RA signaling pathway in the kidney and thereby leads to podocyte damage remains an unknown area. This study aims to explore whether Cd induces podocyte damage by disrupting the RA signaling pathway and to deeply analyze its downstream molecular mechanisms.
We established in vivo Cd-exposed mouse models and in vitro cultured mouse podocyte line models. Podocyte injury is evaluated by detecting proteinuria, key markers of podocytes and assessing the integrity of the cytoskeleton. The local RA levels and the expression of key metabolic enzymes were detected by high performance ELISA and qPCR, respectively. Autophagy markers were monitored by Western Blot to evaluate the autophagy flow status. To resolve the signaling pathways, we intervened with exogenous retinoic acid, the CYP26 inhibitor Talarozole and the RXR antagonist HX531.
Cd exposure induced injury models in mice and podocytes, manifested as significant proteinuria, down-regulation of podocyte marker expression and cytoskeletal destruction. Cd significantly reduced the local RA levels in kidney tissues and podocytes and altered the expression of RA metabolic enzyme CYP26A1. Surprisingly, despite the decrease in RA levels, enhancing RA signaling by supplementing exogenous RA or inhibiting its degradation failed to alleviate Cd-induced podocyte damage. In sharp contrast, inhibiting RXR can strongly rescue podocyte damage, restore the expression of key proteins, and improve the cytoskeletal structure. Mechanistically, we found that Cd exposure led to the obstruction of autophagic flow. The inhibition of RXR can not only reverse podocyte damage but also effectively restore normal autophagic flow. Functionally, the protective effect of inhibiting RXR is superior to that of direct autophagy regulators, indicating that the abnormal activation of RXR is located upstream of autophagy dysfunction.
This study reveals a brand-new mechanism of Cd-induced glomerular toxicity. Cd exposure does not mainly cause damage by leading to RA deficiency, but rather by abnormally activating RXR, which in turn blocks autophagic flux and ultimately leads to podocyte damage and proteinuria. This discovery challenges the traditional view that “RA deficiency causes disease” and establishes RXR as a potential therapeutic target. Our work provides a new paradigm for understanding how environmental heavy metals interfere with nuclear receptor signaling pathways to cause diseases, and also offers a new strategic direction for the prevention and mitigation of Cd-related glomerular diseases.
