Integration of single-cell and bulk transcriptomics reveals β-hydroxybutyrylation-related signatures in primary...

The pathophysiology of primary open-angle glaucoma (POAG), the most prevalent glaucoma type, is poorly understood. Although it is well known that epigenetic factors affect the progression of POAG, the impact of β-hydroxybutyrylation (Kbhb) on POAG remains unknown. Based on POAG-related datasets (GSE27276, GSE4316, and GSE231749) retrieved from the Gene Expression Omnibus (GEO) database, four biomarkers (FABP5, GLS, PDLIM1, and TAGLN) with a diagnostic value for POAG were identified by combining differential expression analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. Immune infiltration analysis demonstrated significant differences in the infiltration abundances of 10 immune cells between POAG and controls, including regulatory T cells, monocytes, and macrophages, with notable positive correlations between TAGLN expression and these immune cells. Subsequently, single-cell analysis revealed that GLS, PDLIM1, and TAGLN were higher expressed in chondrocytes, smooth muscle cells, and endothelial cells. In addition, in vitro cellular experiments and animal models revealed that the TAGLN expression trend was consistent with the data from GSE27276 and GSE4316. In conclusion, TAGLN may play an important role in understanding of the molecular mechanisms of POAG and exploration of therapeutic targets.