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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 global burden of chronic kidney disease (CKD) continues to escalate. Fine particulate matter (PM2.5)has been identified as a significant risk factor for CKD onset, progression, and mortality. However, the underlying mechanisms remain unclear. We have demonstrated that PM2.5 exposure leads to its deposition in renal proximal tubular cells (PTCs) of mice, causing structural damage and functional impairment. We find that pyruvate dehydrogenase kinase 4(PDK4)-mediated energy metabolism dysfunction and epigenetic modifications in PTCs may play a crucial role.
Previous studies by our research group utilizing RNA-seq, phosphoproteomic analysis, and single-cell sequencing have revealed that PDK4 is specifically upregulated in mice PTC cells. This upregulation inhibits the activity of its downstream substrate PDHA1(pS232), thereby stalling the mitochondrial tricarboxylic acid (TCA) cycle and resulting in cellular metabolic impairment. This project utilizes Pdk4 knockout mice, overexpression/ knockout HK-2 cell lines, and techniques like ChIP-seq,metabolic flux analysis, metabolomic mass spectrometry, and in vivo adeno-associated virus intervention to comprehensively analyze the coupling mechanisms of PDK4-regulated metabolic switching and Lactylation.
PM2.5 exposure reprograms mice PTC metabolism. KEGG/GO and GSEA showed predominant metabolic pathway involvement, with suppression of fatty acid β-oxidation, activation of glycolysis, and minimal impact on amino acid metabolism. Metabolite profiling confirmed glucose–lipid dysregulation and a glycolytic shift. Mechanistically, PM2.5 induced PDK4 upregulation and PDHA1 (Ser232) phosphorylation, indicating PDHc inhibition. Pharmacologic PDK4 blockade or genetic deletion relieved TCA cycle impairment, curtailed excessive glycolysis, restored oxidative respiration , and reduced lactate accumulation, apoptosis, and oxidative stress—identifying PDK4 as a key metabolic node. Elevated lactate coincided with increased protein lactylation, specifically histone H4K12 lactylation enriched at transcription start sites. Integrative RNA-seq/ChIP-seq analysis linked H4K12la to upregulation of key glycolytic (PFKP, LDHA) genes.
This study identifies a PDK4–lactate–H4K12la metabolic/epigenetic axis whereby PM2.5-triggered mitochondrial dysfunction drives lactate accumulation, site-specific H4K12 lactylation, and transcriptional upregulation of glycolytic pathways; these insights nominate PDK4 and lactylation dynamics as therapeutic entry points for PM2.5-related kidney injury.
