Scholarlink

Background <p>Polycystic ovary syndrome (PCOS) is a common endocrine disorder with significant impacts on women’s reproductive health. Interleukin (IL)-2 receptor subunit gamma (IL2RG), a common receptor for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, has been shown to interrupt estrous cycle, yet its role in PCOS remains unclear.</p> Results <p>The evaluated expression levels of IL2RG in human granulosa cells (GCs) and IL2RG-dependent cytokines (IL-2, IL-4, IL-15) in follicular fluid were demonstrated in 18 PCOS patients and 22 control subjects. The positive correlation between IL2RG and PCOS was analysed through GEO databases. In vivo, we found that in the PCOS model (6&#xa0;mg/100&#xa0;g body-weight of dehydroepiandrosterone subcutaneous injection for 21 days), the ovarian index, testosterone, glucose, and LH/FSH levels were elevated, and the estrous cycle was disrupted. Knocking down IL2RG (KO) restored the above levels. However, in the dehydroepiandrosterone-treated group, these levels did not recover even after IL2RG was knocked-down. The decreased expression of Gasdermin E (GSDME) but increased caspase-3 level in IL2RG KO rats compared with WT were found. In vitro, knockdown of IL2RG by siRNA inhibited caspase-3-mediated GSDME cleavage in testosterone-induced KGN cells. Furthermore, the caspase-3 inhibitor Z-DEVD-FMK and the caspase-1 inhibitor Belnacasan alleviated pyroptosis in testosterone-induced KGN cells by lactate dehydrogenase test, fluorescence assay, and flow cytometry.</p> Conclusions <p>IL2RG is expressed higher in PCOS patients, exerting an inhibitory effect on caspase-3-mediated GSDME cleavage upon knockdown. However, the knockout of IL2RG led to the conversion of GSDME-mediated pyroptosis into apoptosis. This study explores the function of IL2RG and provides insights for therapeutic targets in PCOS.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

IL2RG knockout mitigates polycystic ovary syndrome pathogenesis by transitioning pyroptosis to apoptosis through the GSDME pathway

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月19日

查看全文
  • Sailing Chen,
  • Han Lu,
  • Yingfen Ying,
  • Haitao Xi,
  • Jingyi Zheng,
  • Chaochao Gong,
  • Shaowei Wang,
  • Yunbin Tang,
  • Junzhao Zhao,
  • Ren-shan Ge,
  • Xiaoheng Li

摘要

Background

Polycystic ovary syndrome (PCOS) is a common endocrine disorder with significant impacts on women’s reproductive health. Interleukin (IL)-2 receptor subunit gamma (IL2RG), a common receptor for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, has been shown to interrupt estrous cycle, yet its role in PCOS remains unclear.

Results

The evaluated expression levels of IL2RG in human granulosa cells (GCs) and IL2RG-dependent cytokines (IL-2, IL-4, IL-15) in follicular fluid were demonstrated in 18 PCOS patients and 22 control subjects. The positive correlation between IL2RG and PCOS was analysed through GEO databases. In vivo, we found that in the PCOS model (6 mg/100 g body-weight of dehydroepiandrosterone subcutaneous injection for 21 days), the ovarian index, testosterone, glucose, and LH/FSH levels were elevated, and the estrous cycle was disrupted. Knocking down IL2RG (KO) restored the above levels. However, in the dehydroepiandrosterone-treated group, these levels did not recover even after IL2RG was knocked-down. The decreased expression of Gasdermin E (GSDME) but increased caspase-3 level in IL2RG KO rats compared with WT were found. In vitro, knockdown of IL2RG by siRNA inhibited caspase-3-mediated GSDME cleavage in testosterone-induced KGN cells. Furthermore, the caspase-3 inhibitor Z-DEVD-FMK and the caspase-1 inhibitor Belnacasan alleviated pyroptosis in testosterone-induced KGN cells by lactate dehydrogenase test, fluorescence assay, and flow cytometry.

Conclusions

IL2RG is expressed higher in PCOS patients, exerting an inhibitory effect on caspase-3-mediated GSDME cleavage upon knockdown. However, the knockout of IL2RG led to the conversion of GSDME-mediated pyroptosis into apoptosis. This study explores the function of IL2RG and provides insights for therapeutic targets in PCOS.