STAT3-derived EIF4E3 promotes H2O2-induced human trabecular meshwork cell injury by activating TGF-β-SMAD2/3 pathway

The dysfunction of HTM cells involves key functions in the pathogenesis of glaucoma. In this study, we aimed to explore the functions of EIF4E3 and its regulatory mechanism in HTM cell injury, thereby illustrating the potential role of EIF4E3 in glaucoma. H 2 O 2 -treated HTM cells were adopted to mimic the glaucoma pathological condition in vitro. Functional experiments were performed using MTT, EdU, and flow cytometry assays, respectively. Oxidative stress was assessed by measuring the levels of superoxide dismutase (SOD) and malondialdehyde (MDA). The interaction between STAT3 and EIF4E3 was verified using dual-luciferase reporter and ChIP assays. EIF4E3 expression was increased in HTM cells after H 2 O 2 treatment. Functionally, EIF4E3 knockdown reversed H 2 O 2 -induced HTM cell apoptosis, oxidative injury and fibrotic changes. Mechanistically, STAT3 promoted EIF4E3 expression by binding to the promoter of EIF4E3. STAT3 could abolish H 2 O 2 -induced HTM cell injury, which was rescued by EIF4E3 up-regulation. In addition, STAT3 bound to EIF4E3 to active the TGF-β-SMAD2/3 pathway. The inhibitor of TGF-β receptor I kinase SD-208 could abate EIF4E3 elevation-evoked boost on H 2 O 2 -induced HTM cell injury. STAT3 bound to EIF4E3 to active TGF-β-SMAD2/3 pathway, and then promoted H 2 O 2 -induced apoptosis, oxidative injury and fibrosis in HTM cells.