Bmal1 promotes prostaglandin E2 synthesis by upregulating Ptgs2 transcription in response to increasing estradiol levels in day 4 pregnant mice
| العنوان: | Bmal1 promotes prostaglandin E2 synthesis by upregulating Ptgs2 transcription in response to increasing estradiol levels in day 4 pregnant mice |
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| المؤلفون: | Jing Zhang, Meina Wu, Yaping Jin, Lijia Zhao, Linlin Zhang, Aihua Wang, Hsu Wen Chao, Luda Yang, Haizhen Jiang, Yaoyao Xiao, Huatao Chen, Xiaoyu Wang, Tiantian Ma |
| المصدر: | American Journal of Physiology-Endocrinology and Metabolism. 320:E747-E759 |
| بيانات النشر: | American Physiological Society, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, endocrine system, Reporter gene, Gene knockdown, medicine.medical_specialty, Physiology, Chemistry, Endocrinology, Diabetes and Metabolism, Uterus, Prostaglandin, PER2, CLOCK, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Endocrinology, medicine.anatomical_structure, Physiology (medical), Internal medicine, medicine, Luciferase, Prostaglandin E2, 030217 neurology & neurosurgery, medicine.drug |
| الوصف: | Prostaglandin G/H synthase 2 (PTGS2) is a rate-limiting enzyme in prostaglandin synthesis. The present study assessed the role of the uterine circadian clock on Ptgs2 transcription in response to steroid hormones during early pregnancy. We demonstrated that the core clock genes (Bmal1, Per2, Nr1d1, and Dbp), Vegf, and Ptgs2, and their encoded proteins, have rhythmic expression in the mouse uterus from days 3.5 to 4.5 (D3.5-4.5) of pregnancy. Progesterone (P4) treatment of cultured uterus endometrial stromal cells (UESCs) isolated from mPer2Luciferase reporter gene knock-in mice on D4 induced a phase shift in PER2::LUCIFERASE oscillations. This P4-induced phase shift of PER2::LUCIFERASE oscillations was significantly attenuated by the P4 antagonist RU486. Additionally, the amplitude of PER2::LUCIFERASE oscillations was increased by estradiol (E2) treatment in the presence of P4. Consistently, the mRNA levels of clock genes (Bmal1 and Per2), Vegf, and Ptgs2 were markedly increased by E2 treatment of UESCs in the presence of P4. Treatment with E2 also promoted prostaglandin E2 (PGE2) synthesis by UESCs. Depletion of Bmal1 in UESCs by small-interfering RNA (siRNA) decreased the transcript levels of clock genes (Nr1d1 and Dbp), Vegf, and Ptgs2 compared with nonsilencing siRNA treatment. Bmal1 knockdown also inhibited PGE2 synthesis. Moreover, the mRNA expression levels of clock genes (Nr1d1 and Dbp), Vegf, and Ptgs2, and their respective proteins were significantly decreased in the uterus of Bmal1-/- mice. Thus, these data suggest that Bmal1 in mice promotes PGE2 synthesis by upregulating Ptgs2 in response to increases in E2 on D4 of pregnancy.NEW & NOTEWORTHY Rhythmic expression of Bmal1 and Ptgs2 was observed in the uterus isolated from D3.5-4.5 of pregnant mice. E2 increased the expression of Bmal1 and Ptg2 in UESCs isolated from mice on D4. The expression of Ptgs2 was significantly decreased in Bmal1-siRNA treated UESCs. Bmal1 knockdown also inhibited PGE2 synthesis. Thus, these data suggest that Bmal1 in mice promotes PGE2 synthesis by upregulating Ptgs2 in response to increases in E2 on D4 of pregnancy. |
| تدمد: | 1522-1555 0193-1849 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::553de0cb0478e87db353d66d33078201 https://doi.org/10.1152/ajpendo.00466.2020 |
| رقم الأكسشن: | edsair.doi...........553de0cb0478e87db353d66d33078201 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221555 01931849 |
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