A multi-omics study reveals molecular characteristics and therapeutic targets of salidroside in reducing TGF-β2-induced ECM expression.

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide, driven by elevated intraocular pressure (IOP) due to trabecular meshwork (TM) fibrosis, extracellular matrix (ECM) accumulation, and increased aqueous humor outflow resistance. Transforming growth factor-beta 2 (TGF-β2) promotes the expression of fibrosis-related genes, exacerbating these effects. Salidroside, a bioactive compound, has been shown to inhibit TGF-β2-induced ECM expression and alleviate ocular hypertension. However, its underlying molecular mechanisms remain unclear. This study explores the transcriptional, proteomic, and metabolic changes in human TM cells treated with TGF-β2 and salidroside. Human TM cells were treated with TGF-β2 (5 ng/mL) for 48 h, followed by salidroside (30 μM) for 24 h. Multi-omics analyses, including transcriptomics, label-free proteomics, and non-targeted metabolomics, were performed to identify differentially expressed genes (DEGs), proteins (DEPs), and metabolites. The results revealed that TGF-β2 inhibited HTM cell metabolism, affecting pathways like the TCA cycle. Salidroside restores balance by regulating 15 key biomolecules, including MELTF and SLC25A10, through dual-level and post-translation mechanisms. ROC and docking analyses highlight salidroside's role in enhancing metabolic transport and energy activity, with SLC25A10 also linked to RNA processing, showcasing its therapeutic potential. These findings provide valuable insights into POAG pathogenesis and the therapeutic potential of salidroside, offering a foundation for the future development of novel treatment strategies targeting transcriptional, translational, and metabolic dysregulation in POAG.