CREBRF regulates apoptosis and estradiol via ISG15/ISGylation in pig granulosa cells

文献类型： 外文期刊

第一作者： Liu, Ying

作者： Liu, Ying;Guo, Xiaorong;Fan, Jiazhen;Xie, Chundi;Fu, Yaxin;Zhou, Rong;Guo, Xiaorong;Liu, Ying;Huang, Tao;Fu, Yaxin;Zhou, Rong

作者机构：

关键词： CREBRF; Apoptosis; Estradiol; Granulosa cells; Pig

期刊名称：FREE RADICAL BIOLOGY AND MEDICINE （ 影响因子：8.2； 五年影响因子：8.6 ）

ISSN： 0891-5849

年卷期： 2024 年 225 卷

页码：

收录情况： SCI

摘要： Granulosa cells play a crucial role in the reproductive processes of female animals, as their proliferation, apoptosis, and hormonal secretion are vital for follicular development and ovulation. Although the role and mechanisms of CREBRF in the reproductive system have been partly reported, its functions in ovarian granulosa cells have not been fully explored. In this study, the results indicated that the expression of CREBRF in the ovaries at 30 days after birth was significantly higher than that during puberty and sexual maturity. Studies on the function of CREBRF found that CREBRF could enhance the synthesis of estradiol and had no effect on progesterone synthesis in pig granulosa cells. At the same time, CREBRF could suppress apoptosis through the Bax/ caspase3/caspase9 pathway and modulation of ISG15/ISGylation in pig granulosa cells. During this process, the expression of many genes changed in granulosa cells. Several genes (CMPK2, MX1, MX2, ZBP1, PML, CHAC1, and BAX) which were promoted apoptosis, were upregulated after CREBRF knockdown with siRNA. ISG15protein conjugation genes (HERC5, UBA7, UBE2L6, ISG15) were also were upregulated. On the contrary, the expression of anti-apoptotic (RFK, SNAP23) genes decreased. In conclusion, CREBRF could enhance the synthesis of estradiol and acted as anti-apoptosis role in pig granulosa cells. This discovery can provide novel insights for further elucidating the molecular mechanisms of granulosa cells in the ovary and potentially identifies CREBRF as a molecular target for improving fertility.

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