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

Yongshun Liang1, Qingqiao Gan1, Xin Zhong1

  • 1Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.

PubMed
Abstract

Insights

Senescence marker protein 30 (SMP30) is downregulated in cataract cell pyroptosis. Overexpressing SMP30 reduces lens epithelial cell pyroptosis by decreasing p-STAT3, showing potential for cataract treatment.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Molecular Medicine

Background:

  • Cataracts are a leading cause of blindness, characterized by lens opacity.
  • Lens epithelial cell (LEC) pyroptosis is implicated in cataract pathogenesis.
  • The role of senescence marker protein 30 (SMP30) in LEC pyroptosis remains unclear.

Purpose of the Study:

  • To investigate the effect of SMP30 on pyroptosis in lens epithelial cells.
  • To determine the relationship between SMP30 and p-STAT3 signaling in cataract development.
  • To explore the therapeutic potential of SMP30 in cataracts.

Main Methods:

  • Cataract induction in rats using UVB irradiation and subsequent analysis of LECs.
  • Quantification of SMP30 and pyroptosis markers using RT-qPCR.
  • Overexpression of SMP30 in rat and human LECs via AAV2 and lentiviral vectors.
  • Proteomic analysis to identify proteins associated with pyroptosis.
  • Western blot, ELISA, and rescue experiments with p-STAT3 modulators.

Main Results:

  • UVB irradiation decreased SMP30 expression and increased pyroptosis markers in rat LECs.
  • SMP30 overexpression reduced pyroptosis markers in H₂O₂-induced human LECs.
  • Proteomic analysis identified STAT3 as a key protein affected by SMP30.
  • Modulation of p-STAT3 signaling influenced the anti-pyroptotic effects of SMP30.

Conclusions:

  • SMP30 expression is downregulated in cataract-associated LEC pyroptosis.
  • Overexpression of SMP30 inhibits LEC pyroptosis, potentially via downregulation of p-STAT3.
  • SMP30 represents a promising target for novel cataract prevention and treatment strategies.

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