Experimental study demonstrates that SMP30 reduces lens epithelial cell pyroptosis by downregulating p-STAT3, suggesting a therapeutic target for cataract prevention.
Background: To determine the effect of senescence marker protein 30 (SMP30) regulation on the levels of p-STAT3 in the pathophysiology of lens epithelial cells (LECs) pyroptosis in cataracts. Methods: Initially, cataracts were induced in rats using ultraviolet B (UVB) irradiation. Transmission electron microscopy was utilized to observe morphological changes in rat LECs, and RT-qPCR was utilized to quantify SMP30 and pyroptosis-related marker genes (GSDMD, Caspase-1, NLRP3, IL-1β, and IL-18). Subsequently, SMP30-AAV2 vectors were injected into the vitreous cavity to overexpress SMP30 in rat lenses. Proteomic analysis identified differential proteins associated with pyroptosis post-SMP30 overexpression. Stable SMP30-overexpressing human LECs (SRA01/04 cells) were established via lentiviral transfection. Western blot, ELISA, and RT-qPCR were used to investigate the role of SMP30 in the pyroptosis of LECs treated with H 2 O 2 . Additionally, rescue experiments with p-STAT3 agonists and inhibitors elucidated SMP30’s molecular mechanisms in H 2 O 2 -induced LECs pyroptosis. Results: After UVB irradiation, SMP30 expression significantly decreased in rat lens capsules, while pyroptosis-related marker gene expression markedly increased. Ten crucial pyroptosis-related proteins were identified by proteomic analysis following SMP30 overexpression, with STAT3 receiving the highest score. SMP30 overexpression during H 2 O 2 -induced pyroptosis in SRA01/04 cells significantly decreased the expression of pyroptosis-related markers (GSDMD, Caspase-1, NLRP3, IL-1β, and IL-18). The p-STAT3 agonist Colivelin weakened the anti-pyroptotic effect of SMP30, while the p-STAT3 inhibitor Stattic enhanced the anti-pyroptotic effect of SMP30. Conclusion: The expression levels of SMP30 were downregulated in cataract cell pyroptosis. When overexpressed, SMP30 can reduce lens epithelial cell pyroptosis by downregulating the expression of p-STAT3. Thus, SMP30 demonstrates promising potential in preventing and treating cataracts.
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Liang et al. (2025) studied this question.
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