FABP3 promotes cell apoptosis and oxidative stress by regulating ferroptosis in lens epithelial cells.

The purpose of this study is to investigate FABP3's biological function and potential mechanism in cataract. Treatment of HO raised FABP3 expression. HO decreased cell viability, enhanced apoptosis, promoted Bax and cleaved caspase-3 expression, inhibited Bcl-2 expression, enhanced the levels of IL-6, IL-1β, and TNF-α, raised MDA level, and decreased SOD and GSH levels in HLE-B3 cells. However, the effects of HO on cell viability, apoptosis, inflammatory cytokines, and oxidative stress were reversed by FABP3 knockdown and aggravated by FABP3 overexpression. HO increased the levels of lipid hydroperoxides and Fe, but reduced the expression of GPX4, SLC7A11, and Ferritin protein. Nevertheless, knockdown of FABP3 reversed the changes of lipid hydroperoxides, Fe, GPX4, SLC7A11, and Ferritin protein, and FABP3 overexpression caused the opposite results. In addition, the inhibition of FABP3 knockdown on cell apoptosis, inflammation, and oxidative stress was reversed by ferroptosis inducer (erastin), and the promotion of FABP3 overexpression on cell apoptosis, inflammation, and oxidative stress was reversed by ferroptosis inhibitor (Fer-1). Taken together, knockdown of FABP3 in lens epithelial cells treated with HO restrained apoptosis, inflammation, and oxidative stress through regulating ferroptosis, suggesting that FABP3 might be a potential target for cataract treatment.