Int Immunopharmacol. 2025 May 10;158:114828. doi: 10.1016/j.intimp.2025.114828. Online ahead of print.
ABSTRACT
Metabolic dysfunction – Associated Steatotic Liver Disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), poses a significant clinical burden due to its high prevalence and potential progression to fibrosis. While neutrophil extracellular traps (NETs) have been implicated in MASLD progression, their specific role in fibrosis remains unclear. This study integrates transcriptomic and single-cell data using weighted gene co-expression network analysis (WGCNA), causal WGCNA (CWGCNA), single-sample gene set enrichment analysis (ssGSEA), gene set variation analysis (GSVA), and linear models for microarray data (Limma) to identify key genes driving steatosis-to-fibrosis transition. Validation in human serum, mouse liver tissue, and mouse serum confirmed that SERPINE1 and THBS1 as robust non-invasive biomarkers with strong diagnostic performance. When combined with clinical features, these markers improved fibrosis prediction accuracy in MASLD patients. Additionally, SERPINE1 appears to mediate interactions between hepatic stellate cells and neutrophils, highlighting a novel therapeutic target. Overall, our findings reveal that NETs-related genes, particularly SERPINE1 and THBS1, hold strong diagnostic value for early-stage fibrosis in MASLD. Targeting SERPINE1 in hepatic stellate cells offers a promising strategy for therapeutic intervention. This study provides a novel framework for non-invasive MASLD fibrosis prediction and lays the foundation for targeted interventions to mitigate disease progression.
PMID:40349409 | DOI:10.1016/j.intimp.2025.114828
