Multi-omics analysis unveils the role of lipid metabolism-derived acylation modifications in POAG and its potential implications
Year: 2025
Type: article
Abstract: Objective: Primary open-angle glaucoma (POAG) is a leading cause of vision loss, with lipid metabolism implicated in its pathogenesis. Our study explores lipid metabolism-derived acylation modifications in POAG using GEO, GWAS, and PubChem databases. Methods: Integrated multi-omics approaches were employed: Mendelian randomization assessed causal relationships between lipid traits and POAG risk; transcriptomic analysis (gene set variation analysis, weighted gene co-expression network analysis) identified key acylation-related genes; machine learning selected feature genes; and single-cell sequencing validated mechanisms in human trabecular meshwork samples. Results: Four lipid metabolism-derived acylations (palmitoylation, myristoylation, succinylation, malonylation) were significantly upregulated in POAG. Core genes 5'-aminolevulinate synthase 2 (ALAS2) and phospholipase C epsilon 1 (PLCE1) were mechanistically linked: ALAS2 catalyzed acyl-CoA accumulation, while myristoylated PLCE1 promoted trabecular fibrosis via collagen type IV alpha 3 chain interaction. External datasets confirmed these findings. Conclusion: Lipid-derived acylations drive POAG through ALAS2-mediated acyl-CoA production and PLCE1-induced fibrosis, revealing novel targets for intervention. Lipid metabolism-derived acylation modifications, particularly succinylation, propionylation, and myristoylation, may play a crucial role in POAG. These findings highlight the potential role of acylation modifications in POAG and offer new insights into POAG's molecular mechanisms and potential research directions.
Authors: Sijie Zhao, Che Xu, Qing Dai, Ziqing Gao, Jian Chen
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,650
OpenAlex ID: W4417524139