<p>Age-related cataract (ARC) is a degenerative change following the aging of the lens, with its specific pathogenesis still unclear. This study investigates the expression of GSK-3β, DNMT3B, and GJA3 in ARC through in vivo and in vitro studies, elucidating the regulatory mechanisms among them. Additionally, it preliminarily explores the role of DNMT3B in the epigallocatechin gallate (EGCG)-mediated delay of apoptosis in lens epithelial cells (LECs). Immunohistochemistry and Western blot results showed that the protein expression level of DNMT3B was elevated, while the protein expression levels of GJA3 and p-GSK-3β (Ser9) were decreased in the ARC group and the aged mouse group (<i>P</i> &lt; 0.05). CCK-8 and Hoechst 333,42 apoptosis assays indicated that DNMT3B, GJA3, and p-GSK-3β (Ser9) were involved in H<sub>2</sub>O<sub>2</sub>-induced apoptosis of LECs. Further investigation revealed that DNMT3B regulates lens epithelial cell apoptosis by modulating GJA3 expression, and the expression of DNMT3B is regulated by GSK-3β. Additionally, we found that EGCG effectively alleviates DNMT3B-mediated apoptosis of LECs (<i>P</i> &lt; 0.05). In summary, our study indicates that p-GSK-3β, DNMT3B, and GJA3 play significant roles in ARC and oxidative stress-induced apoptosis of LECs, with interrelated regulatory mechanisms. EGCG can target DNMT3B to reduce apoptosis in LECs, offering a new direction for the development of cataract treatments.</p>

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The role of DNMT3B, GSK-3β and GJA3 in lens epithelial cell apoptosis and age-related cataract

  • Xiaoya Chen,
  • Dongmei Su,
  • Gaobo Zhang,
  • Zihan Xiang,
  • Yanjiang Fu,
  • Zhaoyi Sun,
  • Yuzhu Hu,
  • Sijia Li,
  • Yue Zhang,
  • Xu Ma,
  • Shanshan Hu,
  • Qianqiu Wei

摘要

Age-related cataract (ARC) is a degenerative change following the aging of the lens, with its specific pathogenesis still unclear. This study investigates the expression of GSK-3β, DNMT3B, and GJA3 in ARC through in vivo and in vitro studies, elucidating the regulatory mechanisms among them. Additionally, it preliminarily explores the role of DNMT3B in the epigallocatechin gallate (EGCG)-mediated delay of apoptosis in lens epithelial cells (LECs). Immunohistochemistry and Western blot results showed that the protein expression level of DNMT3B was elevated, while the protein expression levels of GJA3 and p-GSK-3β (Ser9) were decreased in the ARC group and the aged mouse group (P < 0.05). CCK-8 and Hoechst 333,42 apoptosis assays indicated that DNMT3B, GJA3, and p-GSK-3β (Ser9) were involved in H2O2-induced apoptosis of LECs. Further investigation revealed that DNMT3B regulates lens epithelial cell apoptosis by modulating GJA3 expression, and the expression of DNMT3B is regulated by GSK-3β. Additionally, we found that EGCG effectively alleviates DNMT3B-mediated apoptosis of LECs (P < 0.05). In summary, our study indicates that p-GSK-3β, DNMT3B, and GJA3 play significant roles in ARC and oxidative stress-induced apoptosis of LECs, with interrelated regulatory mechanisms. EGCG can target DNMT3B to reduce apoptosis in LECs, offering a new direction for the development of cataract treatments.