Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells
Autor: | Viktoria von Schönfeldt, Christina Kuhn, Theresa M. Kolben, S Meister, Kritika Sudan, Udo Jeschke, S Beyer, Stefanie Corradini, Sven Mahner, Christian Schulz, Sophie Mitter, L Hahn, Thomas Kolben, Corinna Paul |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
PPARγ
Pyridines Epigenesis Genetic Histones Pre-Eclampsia Pregnancy Protein Isoforms histone modification Biology (General) Spectroscopy biology Chemistry General Medicine Computer Science Applications Cell biology Trophoblasts Histone medicine.anatomical_structure embryonic structures Benzamides Female Signal Transduction Adult H3K9ac placenta QH301-705.5 Retinoid X receptor Methylation Catalysis Article Inorganic Chemistry preeclampsia Histone H3 Placenta medicine Humans Epigenetics ddc:610 Physical and Theoretical Chemistry Molecular Biology QD1-999 Retinoid X Receptor alpha Organic Chemistry Trophoblast H3K4me3 PPAR gamma Acetylation Case-Control Studies biology.protein RxRα Thiazolidinediones |
Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 22 International Journal of Molecular Sciences, Vol 22, Iss 12469, p 12469 (2021) |
ISSN: | 1422-0067 |
Popis: | The aim of this study was to analyze the expression of peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RxRα), a binding heterodimer playing a pivotal role in the successful trophoblast invasion, in the placental tissue of preeclamptic patients. Furthermore, we aimed to characterize a possible interaction between PPARγ and H3K4me3 (trimethylated lysine 4 of the histone H3), respectively H3K9ac (acetylated lysine 9 of the histone H3), to illuminate the role of histone modifications in a defective trophoblast invasion in preeclampsia (PE). Therefore, the expression of PPARγ and RxRα was analyzed in 26 PE and 25 control placentas by immunohistochemical peroxidase staining, as well as the co-expression with H3K4me3 and H3K9ac by double immunofluorescence staining. Further, the effect of a specific PPARγ-agonist (Ciglitazone) and PPARγ-antagonist (T0070907) on the histone modifications H3K9ac and H3K4me3 was analyzed in vitro. In PE placentas, we found a reduced expression of PPARγ and RxRα and a reduced co-expression with H3K4me3 and H3K9ac in the extravillous trophoblast (EVT). Furthermore, with the PPARγ-antagonist treated human villous trophoblast (HVT) cells and primary isolated EVT cells showed higher levels of the histone modification proteins whereas treatment with the PPARγ-agonist reduced respective histone modifications. Our results show that the stimulation of PPARγ-activity leads to a reduction of H3K4me3 and H3K9ac in trophoblast cells, but paradoxically decreases the nuclear PPARγ expression. As the importance of PPARγ, being involved in a successful trophoblast invasion has already been investigated, our results reveal a pathophysiologic connection between PPARγ and the epigenetic modulation via H3K4me3 and H3K9ac in PE. |
Databáze: | OpenAIRE |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |