2. Academic Validation
  3. SMP30 Attenuates Lens Epithelial Cells Pyroptosis of Cataract via the Downregulation of p-STAT3

SMP30 Attenuates Lens Epithelial Cells Pyroptosis of Cataract via the Downregulation of p-STAT3

  • J Inflamm Res. 2025 Sep 8:18:12361-12377. doi: 10.2147/JIR.S536127.
Yongshun Liang 1,  Qingqiao Gan 1,  Xin Zhong 1,  Tian Lan 1,  Yingqin Yang 2,  Lixia Lin 1,  Chengye Tang 1,  Hao Liang 1
Affiliations

Affiliations

  • 1 Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
  • 2 Department of Ophthalmology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People's Republic of China.
PMID: 40951443 DOI: 10.2147/JIR.S536127
Abstract

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 H2O2. Additionally, rescue experiments with p-STAT3 agonists and inhibitors elucidated SMP30's molecular mechanisms in H2O2-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 H2O2-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.

Keywords

SMP30; cataract; lens epithelial cells; p-STAT3; pyroptosis.

Figures
Products