Elabela: Negative Regulation of Ferroptosis in Trophoblasts via the Ferritinophagy Pathway Implicated in the Pathogenesis of Preeclampsia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Participants and Sample Collection
2.2. Animal
2.3. Cell Culture
2.4. Transfection
2.5. Immunohistochemistry
2.6. Perls’ Prussian Blue Staining
2.7. H&E Staining
2.8. Assay for GSH, MDA and Iron
2.9. Elabela Elisa
2.10. RNA Extraction and RT-qPCR
2.11. Cell Counting Kit-8 Assay
2.12. Determination of Reactive Oxygen Species
2.13. Assessment of Lipid Peroxidation
2.14. Cellular Labile Iron Detection
2.15. Cellular Lysosomes Detection
2.16. Transmission Electron Microscopy
2.17. Autophagy Flux Analysis
2.18. Western Blotting
2.19. Matrigel Invasion Assay
2.20. Wound Healing Assay
2.21. DNA Synthesis Assay
2.22. mRNA Sequencing
2.23. Statistical Analyses
3. Results
3.1. More Severe Ferroptosis Presented in the Placentas of PE
3.2. Low Levels of Elabela in the Placenta and Circulation of the Pregnancy with Preeclampsia
3.3. The PE-like and Ferroptosis Phenotypes in Mice Were Relieved by Elabela Administration
3.4. Erastin and RSL3 Induce HTR-8/SVneo Death in a Time-Dose-Dependent Manner
3.5. Elabela Can Rescue Ferroptosis Induced by Erastin
3.6. Elabela Could Reduce Erastin-Exacerbated Oxidative Stress and Lipid Peroxidation, and Rescue Cell Dysfunction
3.7. Ferroptosis Is an Autophagy-Dependent form of Cell Death
3.8. Ferritinophagy Is Involved in Ferroptosis in Trophoblasts
3.9. The Ferritinophagy Pathway Plays a Role in the Regulation of Ferroptosis by Elabela
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
List of Abbreviation
PE | Preeclampsia |
ELA | Elabela |
FGR | Fetal growth restriction |
AngII | Angiotensin II |
APJ | Angiotensin II type 1 receptor-related protein |
PI3K | Phosphatidylinositol 3-kinase |
AKT | Protein kinase B |
ACOG | American College of Obstetricians and Gynecologists |
LIP | Labile iron pool |
GSH | Glutathione |
MDA | Malondialdehyde |
IHC | Immunohistochemistry |
4-HNE | 4-Hydroxynonenal |
ELISA | Enzyme-linked immunosorbent assay |
RT-qPCR | Real-time quantitative polymerase chain reaction |
CCK8 | Cell counting kit-8 |
ROS | Reactive oxygen species |
WB | Western blotting |
CTB | Cytotrophoblast |
STB | Syncytiotrophoblast |
iEVT | Interstitial extravillous trophoblast |
3-MA | 3-Methyladenine |
CQ | Chloroquine |
EdU | 5-Ethynyl-2’-deoxyuridine |
MOI | Multiplicity of infection |
Ad | Adenovirus |
OE | Overexpression |
GO | Gene Ontology |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
GSEA | Gene Set Enrichment Analysis |
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Yang, H.; Zhang, X.; Ding, Y.; Xiong, H.; Xiang, S.; Wang, Y.; Li, H.; Liu, Z.; He, J.; Tao, Y.; et al. Elabela: Negative Regulation of Ferroptosis in Trophoblasts via the Ferritinophagy Pathway Implicated in the Pathogenesis of Preeclampsia. Cells 2023, 12, 99. https://doi.org/10.3390/cells12010099
Yang H, Zhang X, Ding Y, Xiong H, Xiang S, Wang Y, Li H, Liu Z, He J, Tao Y, et al. Elabela: Negative Regulation of Ferroptosis in Trophoblasts via the Ferritinophagy Pathway Implicated in the Pathogenesis of Preeclampsia. Cells. 2023; 12(1):99. https://doi.org/10.3390/cells12010099
Chicago/Turabian StyleYang, Huan, Xuemei Zhang, Yubin Ding, Hui Xiong, Shaojian Xiang, Yang Wang, Huanhuan Li, Zheng Liu, Jie He, Yuelan Tao, and et al. 2023. "Elabela: Negative Regulation of Ferroptosis in Trophoblasts via the Ferritinophagy Pathway Implicated in the Pathogenesis of Preeclampsia" Cells 12, no. 1: 99. https://doi.org/10.3390/cells12010099