HERC5-mediated ubiquitination of IGFBP3 drives the inflammatory response and cell apoptosis in dry eye syndrome

Background Dry eye syndrome is a common chronic ocular surface disease. Immune disorders, oxidative stress and excessive apoptosis of human corneal epithelial cells are the key pathological mechanisms of dry eye. The role and core regulatory molecules of ubiquitination in the pathogenesis of dry eye remain unclear. Objective This study aims to screen the key ubiquitination molecules related to dry eye syndrome, reveal its regulatory mechanism, and provide new targets for clinical diagnosis and treatment. Methods The core genes were screened by transcriptomics, weighted gene co-expression network analysis, and the key ubiquitinating enzymes were identified via bioinformatics analysis. siRNA interference, co-immunoprecipitation, ubiquitination experiment, and rescue experiments were used to verify the regulatory effect of target molecules on inflammation and apoptosis in dry eye model. Results The HECT and RLD domain containing E3 ubiquitin protein ligase 5 was ultimately identified as the core molecule, which was correlated with inflammation and apoptosis. HERC5 directly interacted with insulin like growth factor binding protein 3 and promoted the degradation of IGFBP3 through ubiquitination modification. Additionally, knockdown of HERC5 reduced the levels of inflammatory factors and inhibited apoptosis, while knockout of IGFBP3 reversed this protective effect. Conclusion This study clarifies that the HERC5-IGFBP3 axis is a key mechanism in dry eye pathogenesis, providing a new theoretical basis and potential targets for targeted treatment.