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Updated: Aug 6, 2026
Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
Integrated computational analysis identifies FABP4, PTGS2, and HPGD as Key molecular targets linking PET microplastic
1Department of Clinical Laboratory, Pidu District People's Hospital, The 3RD Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
Background:
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 25-38% of the global population, yet the contribution of environmental polyethylene terephthalate (PET) microplastics to its pathogenesis remains unclear. PET microplastics accumulate in the liver at approximately 4.6 particles per gram of tissue and have been implicated in metabolic disturbance, oxidative stress, and inflammation, but their molecular targets and mechanisms in MASLD are not well defined.
Methods:
We integrated three GEO microarray cohorts (GSE37031, GSE63067, GSE89632) and performed differential expression analysis, weighted gene co-expression network analysis (WGCNA), and PET target prediction using ChEMBL, PharmMapper, and SwissTargetPrediction. Functional enrichment, protein-protein interaction network analysis, CIBERSORT-based immune deconvolution, molecular docking, and 100 ns molecular dynamics simulations were employed to identify and validate hub genes.
Results:
Integration of MASLD transcriptomes and PET target predictions yielded 19 overlapping genes enriched in pathways related to lipid metabolism, fatty acid degradation, glycolysis/gluconeogenesis, and chemical carcinogenesis. Network topology consistently highlighted FABP4, PTGS2, and HPGD as central hub genes. Immune deconvolution revealed MASLD-associated alterations characterized by increased M2 macrophages and γδ T cells, with decreased monocytes, dendritic cells, and naive B cells. PTGS2 and FABP4 expression showed strong correlations with innate immune cells. Molecular docking demonstrated favorable PET binding to all three proteins (-6.3 to -6.9 kcal/mol), and molecular dynamics simulations confirmed stable complexes over 100 ns, with predominantly hydrophobic interactions.
Conclusions:
Through integrated bioinformatics analysis and molecular simulation, this study identifies FABP4, PTGS2, and HPGD as potential molecular targets through which PET microplastics may influence lipid metabolism, prostaglandin signaling, and innate immune responses in MASLD. Molecular docking and dynamics simulations suggest favorable binding interactions between PET and these proteins.
Insights
Polyethylene terephthalate (PET) microplastics may drive metabolic dysfunction-associated steatotic liver disease (MASLD) by targeting FABP4, PTGS2, and HPGD. These interactions influence lipid metabolism and immune responses in the liver.
Area of Science:
- Environmental health
- Molecular biology
- Hepatology
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) affects a significant portion of the global population.
- The role of polyethylene terephthalate (PET) microplastics in MASLD pathogenesis is not well understood.
- PET microplastics are found in the liver and linked to metabolic disturbances, oxidative stress, and inflammation.
Purpose of the Study:
- To investigate the molecular targets and mechanisms by which PET microplastics contribute to MASLD.
- To identify key genes and pathways affected by PET microplastic exposure in MASLD.
Main Methods:
- Integrated analysis of three MASLD transcriptomic datasets (GEO cohorts).
- Weighted gene co-expression network analysis (WGCNA) and PET target prediction.
- Functional enrichment, protein-protein interaction, immune deconvolution, molecular docking, and molecular dynamics simulations.
Main Results:
- 19 overlapping genes identified, enriched in lipid metabolism, fatty acid degradation, and glycolysis pathways.
- FABP4, PTGS2, and HPGD identified as central hub genes, with strong correlations to innate immune cells.
- PET microplastics showed favorable binding to FABP4, PTGS2, and HPGD, confirmed by molecular dynamics simulations.
Conclusions:
- FABP4, PTGS2, and HPGD are identified as potential molecular targets of PET microplastics in MASLD.
- PET microplastics may influence lipid metabolism, prostaglandin signaling, and innate immune responses in MASLD.
- Molecular simulations support direct binding interactions between PET and these key proteins.
