SH2B1 promotes apoptosis in diabetic cataract via p38 MAPK pathway

Patients with diabetes face an increased risk of developing cataracts, with unclear mechanisms. Our study illuminates these mechanisms by identifying differentially expressed proteins in the lens anterior capsule of patients with diabetic cataract (DC) and age-related cataract using quantitative proteomics. We found SH2 domain-containing adapter protein B1 (SH2B1) to be crucial in DC progression. Reduced SH2B1 expression was confirmed through PCR and western blotting in patient samples, diet-induced obese mice, and high- glucose (HG)-cultured human lens epithelial cells. Under HG conditions, cell proliferation decreased, while migration and apoptosis, alongside changes in Bcl2 and caspase-3 expression, increased. Overexpressing SH2B1 alleviated these changes and influenced the p38 mitogen-activated protein kinase (MAPK) signaling pathway. This suggests SH2B1 and the p38 MAPK pathway as significant in DC pathogenesis and potential therapeutic targets. Clinically, this could lead to therapies aimed at halting or slowing DC progression.