Induction of TGF‐β receptor I expression in a DNA methylation‐independent manner mediated by DNMT3A downregulation is involved in early‐onset severe preeclampsia
| العنوان: | Induction of TGF‐β receptor I expression in a DNA methylation‐independent manner mediated by DNMT3A downregulation is involved in early‐onset severe preeclampsia |
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| المؤلفون: | Jiqin Zhang, Han Xie, Hao Ying, Yuanhui Jia |
| المصدر: | The FASEB Journal. 34:13224-13238 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, 0301 basic medicine, Receptor, Transforming Growth Factor-beta Type I, Down-Regulation, Smad Proteins, macromolecular substances, SMAD, Biology, Biochemistry, Cell Line, DNA Methyltransferase 3A, Preeclampsia, 03 medical and health sciences, 0302 clinical medicine, Pre-Eclampsia, Downregulation and upregulation, Pregnancy, Transforming Growth Factor beta, Genetics, Trophoblast cell migration, medicine, Humans, Enhancer of Zeste Homolog 2 Protein, DNA (Cytosine-5-)-Methyltransferases, Promoter Regions, Genetic, Molecular Biology, reproductive and urinary physiology, Gene knockdown, EZH2, Trophoblast, DNA Methylation, medicine.disease, female genital diseases and pregnancy complications, Trophoblasts, 030104 developmental biology, medicine.anatomical_structure, embryonic structures, DNA methylation, Cancer research, Female, 030217 neurology & neurosurgery, Signal Transduction, Biotechnology |
| الوصف: | Preeclampsia, especially early-onset severe preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality. Although it has been well known that the pathophysiology of early-onset severe preeclampsia begins with abnormal placentation and aberrant activation of TGF-β signaling inhibits trophoblast cell invasion, the mechanisms underlying dysregulation of TGF-β signaling in early-onset severe preeclampsia remain elusive to date. Here, we revealed that induction of TGFBR1/TGF-β signaling mediated by DNMT3A downregulation plays a critical role in early-onset severe preeclampsia. Our results show that DNMT3A downregulation elevates TGFBR1 expression in trophoblast cells. Moreover, inhibition of TGFBR1 and TGF-β/Smad signaling can rescue the deficiencies of trophoblast cell migration and invasion caused by DNMT3A knockdown. Mechanistically, DNMT3A suppresses the transcription of TGFBR1 through recruiting EZH2 to its promoter but not changing DNA methylation of TGFBR1 promoter. In human samples, we detected lowly expressed DNMT3A, highly expressed TGFBR1 and hyperactivation of TGF-β/Smad signaling in decidua-embedded extravillous trophoblasts in early-onset severe preeclampsia, which provides the clinical evidence for the correlation between DNMT3A and TGFBR1. Collectively, our findings demonstrate that DNA methylation-independent induction of TGFBR1 mediated by DNMT3A downregulation is relevant to the development of early-onset severe preeclampsia. |
| تدمد: | 1530-6860 0892-6638 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6207dc78139c851ad326366484cd5821Test https://doi.org/10.1096/fj.202000253rrTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....6207dc78139c851ad326366484cd5821 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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