NOX4 facilitates diabetic cataract progression through the NF-κB signaling pathway

The study aimed to investigate the functional significance of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) in diabetic cataract (DC). SRA01/04 cells were exposed to different concentrations (5 mmol/L, 55 mmol/L) of glucose solution. Cell viability and apoptosis of SRA01/04 cells were evaluated separately using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Western blot and RT-qPCR were employed to analyze protein and mRNA levels. Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and inflammatory factor levels in SRA01/04 cells were measured by enzyme-linked immunosorbent assay. Elevated NOX4 levels were detected in DC compared to age-related cataract (ARC) patients. In vitro experiments demonstrated that high glucose (HG) resulted in reduced cell viability, enhanced apoptosis, and elevated NOX4 expression in SRA01/04 cells. Overexpression of NOX4 exacerbated these effects, worsening cell viability reduction and apoptosis promotion. Moreover, NOX4 overexpression heightened oxidative stress and inflammation markers. Conversely, NOX4 downregulation improved cell viability, reduced apoptosis, and attenuated oxidative stress and inflammatory responses under HG condition. Mechanistic investigations revealed that inhibition of nuclear factor-kappa B (NF-kappa B) reversed the impacts of NOX4 overexpression on oxidative stress and inflammation, implicating the involvement of NOX4 in the modulation of DC through the NF-kappa B signaling pathway. These discoveries provided important insights into the molecular mechanisms driving DC pathogenesis and underscored the significance of targeting NOX4 as a promising therapeutic strategy for addressing DC.