COPS5 negatively regulates goat endometrial function via the ERN1 and mTOR-autophagy pathways during early pregancy
COPS5 negatively regulates goat endometrial function via the ERN1 and mTOR-autophagy pathways during early pregancy
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COPS5 在妊娠早期通过 ERN1 和 mTOR 自噬途径负向调节山羊子宫内膜功能
DOI：
10.1002/jcp.28505
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发表时间：
2019
影响因子：
5.6
通讯作者：
Jin Yaping
中科院分区：
文献类型：
--
作者：
Yang Diqi;Zhang Beibei;Wang Zongjie;Zhang Linlin;Chen Huatao;Zhou Dong;Tang Keqiong;Wang Aihua;Lin Pengfei;Jin Yaping
在反刍动物中，足够的子宫内膜功能是影响着床和经济效益的主要因素。然而，山羊子宫内膜功能在妊娠着床期的确切调控机制尚不清楚。在此，我们研究了组成型光形态发生蛋白-9信号体（COPS 5）的第五组分在子宫内膜上皮细胞（EECs）中调节子宫内膜功能的功能作用和信号转导。我们的研究结果表明，激素降低COPS 5的表达，以及COPS 5介导的子宫内膜功能调节。我们还发现COPS 5的敲低通过G1期细胞周期阻滞阻碍了EECs的增殖。激素通过激素受体影响COPS 5的活性，而COPS 5表达的反馈调节受体的转录。此外，通过si-ERN 1将内质网（ER）敲低为核信号1（ERN 1），部分抑制了shCOPS 5 EECs中的子宫内膜功能。此外，通过雷帕霉素阻断mTOR通路促进si-ERN 1-转染的shCOPS 5 EECs中的子宫内膜功能。总的来说，这些结果表明COPS 5通过ERN 1和mTOR-自噬途径负调节山羊子宫内膜功能，并为COPS 5在女性生殖发育过程中的机制途径提供了新的见解。
In ruminant, adequate endometrial function is a major factor affecting implantation and economic efficiency. However, the precise mechanisms regulating goat endometrial function during the peri‐implantation period of pregnancy are still unclear. Here, we investigated the functional role and signal transduction of the fifth component of the constitutive photomorphogenic‐9 signalosome (COPS5) in the regulation of endometrial function in endometrial epithelial cells (EECs). Our results showed that hormones decreased COPS5 expression, and COPS5‐mediated regulation of endometrial function. We also found that knockdown of COPS5 hindered EECs proliferation by the G1‐phase cell cycle arrest. Hormones affected the activity of COPS5 through hormones receptors, while feedback from the expression of COPS5 regulated the transcription of the receptor. Moreover, knockdown of endoplasmic reticulum (ER) to nucleus signaling 1 (ERN1) via si‐ERN1 partly inhibited endometrial function in shCOPS5 EECs. In addition, blocking the mTOR pathway by rapamycin promoted endometrial function in si‐ERN1‐transfected shCOPS5 EECs. Overall, these results suggest that COPS5 negatively regulatesgoatendometrial function via the ERN1 and mTOR‐autophagy pathways and provide new insights into the mechanistic pathways of COPS5 during female reproductive development.