Activated PRDM1-CREBBP contributes to preeclampsia by regulating apoptosis and invasion of the human trophoblast cells
Summary: Preeclampsia (PE) is a multifactorial disorder of pregnancy, characterized by new-onset gestational hypertension. High-throughput mRNA sequencing (RNA-seq) was performed to analyze the gene expression patterns in placentas from patients with early-onset PE (EOPE). PR domain zinc-finger prot...
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Elsevier
2024-12-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224027111 |
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| author | Xuan Zhang Lei Sun |
| author_facet | Xuan Zhang Lei Sun |
| author_sort | Xuan Zhang |
| collection | DOAJ |
| description | Summary: Preeclampsia (PE) is a multifactorial disorder of pregnancy, characterized by new-onset gestational hypertension. High-throughput mRNA sequencing (RNA-seq) was performed to analyze the gene expression patterns in placentas from patients with early-onset PE (EOPE). PR domain zinc-finger protein 1 (PRDM1) expression increased in the chorionic villi and placental basal plate from patients with PE and nitro-l-arginine methyl ester (L-NAME)-treated rats. Inhibition of PRDM1 enhanced trophoblast/extravillous trophoblast (EVT) cell invasion/migration and reduced apoptosis under hypoxia/reoxygenation (H/R) conditions. RNA-seq data indicated that the expression of CREB-binding protein (CREBBP), a transcriptional coactivator, was upregulated in preeclamptic placentas and showed a positive correlation with that of PRDM1. Genetic and pharmacological inhibition of CREBBP exhibited anti-apoptotic and pro-invasive roles. H/R stimulation upregulated CREBBP expression and augmented the binding of PRDM1 to CREBBP’s promoter. CREBBP was further validated as a direct downstream target of PRDM1. Collectively, our work reveals an involvement of the activated PRDM1-CREBBP axis in PE-associated trophoblast dysfunction. |
| format | Article |
| id | doaj-art-908acef2e9834ecfa1f84c4a2fb191bf |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-908acef2e9834ecfa1f84c4a2fb191bf2024-12-22T05:29:30ZengElsevieriScience2589-00422024-12-012712111484Activated PRDM1-CREBBP contributes to preeclampsia by regulating apoptosis and invasion of the human trophoblast cellsXuan Zhang0Lei Sun1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, P.R. ChinaDepartment of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, P.R. China; Corresponding authorSummary: Preeclampsia (PE) is a multifactorial disorder of pregnancy, characterized by new-onset gestational hypertension. High-throughput mRNA sequencing (RNA-seq) was performed to analyze the gene expression patterns in placentas from patients with early-onset PE (EOPE). PR domain zinc-finger protein 1 (PRDM1) expression increased in the chorionic villi and placental basal plate from patients with PE and nitro-l-arginine methyl ester (L-NAME)-treated rats. Inhibition of PRDM1 enhanced trophoblast/extravillous trophoblast (EVT) cell invasion/migration and reduced apoptosis under hypoxia/reoxygenation (H/R) conditions. RNA-seq data indicated that the expression of CREB-binding protein (CREBBP), a transcriptional coactivator, was upregulated in preeclamptic placentas and showed a positive correlation with that of PRDM1. Genetic and pharmacological inhibition of CREBBP exhibited anti-apoptotic and pro-invasive roles. H/R stimulation upregulated CREBBP expression and augmented the binding of PRDM1 to CREBBP’s promoter. CREBBP was further validated as a direct downstream target of PRDM1. Collectively, our work reveals an involvement of the activated PRDM1-CREBBP axis in PE-associated trophoblast dysfunction.http://www.sciencedirect.com/science/article/pii/S2589004224027111Cardiovascular medicineCell biology |
| spellingShingle | Xuan Zhang Lei Sun Activated PRDM1-CREBBP contributes to preeclampsia by regulating apoptosis and invasion of the human trophoblast cells iScience Cardiovascular medicine Cell biology |
| title | Activated PRDM1-CREBBP contributes to preeclampsia by regulating apoptosis and invasion of the human trophoblast cells |
| title_full | Activated PRDM1-CREBBP contributes to preeclampsia by regulating apoptosis and invasion of the human trophoblast cells |
| title_fullStr | Activated PRDM1-CREBBP contributes to preeclampsia by regulating apoptosis and invasion of the human trophoblast cells |
| title_full_unstemmed | Activated PRDM1-CREBBP contributes to preeclampsia by regulating apoptosis and invasion of the human trophoblast cells |
| title_short | Activated PRDM1-CREBBP contributes to preeclampsia by regulating apoptosis and invasion of the human trophoblast cells |
| title_sort | activated prdm1 crebbp contributes to preeclampsia by regulating apoptosis and invasion of the human trophoblast cells |
| topic | Cardiovascular medicine Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224027111 |
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