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논문분류	춘계학술대회 초록집
제목	Lactylation Modulates Immune and Metabolic Dysregulation in Anti-Neutrophil Cytoplasmic Antibody Associated Glomerulonephritis
저자	Jingxue Du
출판정보	2025; 2025(1):
키워드	lactylation, bioinformatics, Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis
초록	Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (AAGN) is characterized by immune dysregulation and organ damage. Lactylation, a key modulator of immune-metabolic crosstalk, has not been explored in AAGN. This study aims to elucidate the molecular landscape of lactylation and its clinical implications in immune microenvironment remodeling and renal diagnosis in AAGN. We integrated three transcriptomic datasets (GSE108109/GSE99339/GSE104948) and single-cell sequencing data (GSE250138). Differential expression analysis, WGCNA co-expression networks, and machine learning (Lasso/Random Forest) identified lactylation-related genes. Immune infiltration was assessed via CIBERSORT, consensus clustering defined molecular subtypes, single-cell sequencing resolved cell-specific expression, and TF-miRNA-genes networks were constructed. Five lactylation-driven genes (ALDOB/JPT1/LCP1/LGALS1/RALYL) were identified, with a diagnostic nomogram achieving AUC>0.85. Their expression correlated with GFR and monocyte/M0 macrophage infiltration. Molecular subtyping revealed Subtype2 with enhanced monocyte infiltration and preserved renal function. Single-cell sequencing showed ALDOB/RALYL expressed primarily in tubular cells, while JPT1/LCP1/LGALS1 were upregulated in myofibroblasts. FOXO3/4 potentially regulated ALDOB/RALYL to drive disease progression. This study pioneers the role of lactylation in AAGN, linking lactylation-fibrotic axis and immune crosstalk to disease pathogenesis. The core genes and molecular subtypes offer novel precision diagnosis and therapy tools. Further experimental validation and metabolic-targeted interventions are warranted for clinical translation.
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