Abstract
Syncytin-1 is a protein coded by a human endogenous retrovirus (HERV) gene of the HERV-W family (HERVWE1). Syncytin- 1 mediates formation of syncytiotrophoblasts through fusion of cytotrophoblasts, a hallmark of terminal differentiation of placental trophoblast linage. Syncytin-1 also possesses nonfusogenic functions and regulates cell cycle progression. While decreased syncytin-1 expression and syncytium deficiency are considered important pathological changes in preeclampsia, the molecular mechanism(s) underlying syncytin-1 downregulation remains unclear. In this study, we confirmed that expression levels of syncytin-1 mRNA and protein were significantly lower in preeclamptic placentas compared to normal controls. Human chorionic somatomammotropin expression, a marker for syncytium function, was also decreased in preeclamptic placentas. The mRNA levels of ASCT2, the syncytin-1 receptor involved in cell fusion process, and GCMa, a transcriptional factor known to regulate syncytin-1 expression, were not significantly altered. Methylation in the 5’LTR of syncytin-1 promoter was quantified by COBRA, methylation-specific PCR, and DNA sequencing. Results from all three assays indicated significantly hypermethylated syncytin-1 promoter in preeclamptic placentas compared to normal controls. Methylation levels were inversely correlated with syncytin-1 mRNA levels, suggesting that hypermethylation may lead to syncytin-1 downregulation. Further experiments indicated that DNMT1 and DNMT3B3 mRNA and protein levels were increased in preeclamptic placentas, suggesting that higher DNA methyltransferase activity may contribute to the hypermethylation of syncytin-1 in preeclamptic placentas. These results indicated that aberrant hypermethylation is involved in downregulation of syncytin-1, and epigenetic alterations may play a significant role in the development of preeclampsia.
Keywords: Syncytin-1, DNA methylation, preeclampsia, trophoblast, placenta.
Current Pharmaceutical Design
Title:Decreased Expression and Altered Methylation of Syncytin-1 Gene in Human Placentas Associated with Preeclampsia
Volume: 20 Issue: 11
Author(s): Xue-Wei Zhuang, Jinping Li, Brian C. Brost, Xi-Yan Xia, Hai Bin Chen, Chuan-Xin Wang and Shi-Wen Jiang
Affiliation:
Keywords: Syncytin-1, DNA methylation, preeclampsia, trophoblast, placenta.
Abstract: Syncytin-1 is a protein coded by a human endogenous retrovirus (HERV) gene of the HERV-W family (HERVWE1). Syncytin- 1 mediates formation of syncytiotrophoblasts through fusion of cytotrophoblasts, a hallmark of terminal differentiation of placental trophoblast linage. Syncytin-1 also possesses nonfusogenic functions and regulates cell cycle progression. While decreased syncytin-1 expression and syncytium deficiency are considered important pathological changes in preeclampsia, the molecular mechanism(s) underlying syncytin-1 downregulation remains unclear. In this study, we confirmed that expression levels of syncytin-1 mRNA and protein were significantly lower in preeclamptic placentas compared to normal controls. Human chorionic somatomammotropin expression, a marker for syncytium function, was also decreased in preeclamptic placentas. The mRNA levels of ASCT2, the syncytin-1 receptor involved in cell fusion process, and GCMa, a transcriptional factor known to regulate syncytin-1 expression, were not significantly altered. Methylation in the 5’LTR of syncytin-1 promoter was quantified by COBRA, methylation-specific PCR, and DNA sequencing. Results from all three assays indicated significantly hypermethylated syncytin-1 promoter in preeclamptic placentas compared to normal controls. Methylation levels were inversely correlated with syncytin-1 mRNA levels, suggesting that hypermethylation may lead to syncytin-1 downregulation. Further experiments indicated that DNMT1 and DNMT3B3 mRNA and protein levels were increased in preeclamptic placentas, suggesting that higher DNA methyltransferase activity may contribute to the hypermethylation of syncytin-1 in preeclamptic placentas. These results indicated that aberrant hypermethylation is involved in downregulation of syncytin-1, and epigenetic alterations may play a significant role in the development of preeclampsia.
Export Options
About this article
Cite this article as:
Zhuang Xue-Wei, Li Jinping, Brost C. Brian, Xia Xi-Yan, Chen Bin Hai, Wang Chuan-Xin and Jiang Shi-Wen, Decreased Expression and Altered Methylation of Syncytin-1 Gene in Human Placentas Associated with Preeclampsia, Current Pharmaceutical Design 2014; 20 (11) . https://dx.doi.org/10.2174/13816128113199990541
DOI https://dx.doi.org/10.2174/13816128113199990541 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Genomic Organization and Control of the Grb7 Gene Family
Current Genomics Testicular Germ Cell Tumors: A Paradigm for the Successful Treatment of Solid Tumor Stem Cells
Current Cancer Therapy Reviews Folate Nutrigenetics: A Convergence of Dietary Folate Metabolism, Folic Acid Supplementation, and Folate Antagonist Pharmacogenetics
Drug Metabolism Letters Killing Glioma ‘Stem-like’ Cells via Drug-Induced Relocation of Endosomal Urokinase Proteins
Anti-Cancer Agents in Medicinal Chemistry Sinonasal Carcinoma: Updated Phenotypic and Molecular Characterization
Current Cancer Therapy Reviews Drug Design Targeting the CXCR4/CXCR7/CXCL12 Pathway
Current Topics in Medicinal Chemistry Sodium Dependent Multivitamin Transporter (SMVT): A Potential Target for Drug Delivery
Current Drug Targets 7-O-aminoalkyl-2,3-dehydrosilibinins: Synthesis and in vitro Anti-cancer Efficacy
Anti-Cancer Agents in Medicinal Chemistry Application of MALDI/SELDI Mass Spectrometry to Cancer Biomarker Discovery and Validation
Current Proteomics Recent Advances in New Discovered Molecular Targets in Testicular Germ Cell Tumors
Current Medicinal Chemistry Bioinformatics of Protein-Protein Interfaces and Small Molecule Effectors
Current Bioinformatics Higher Placental Anti-Inflammatory IL-10 Cytokine Expression in HIV-1 Infected Women Receiving Longer Zidovudine Prophylaxis Associated with Nevirapine
Current HIV Research Preface
Current Molecular Medicine The Urokinase Plasminogen Activator System: A Target for Anti-Cancer Therapy
Current Cancer Drug Targets Targeting the Folate Receptor: Improving Efficacy in Inorganic Medicinal Chemistry
Current Medicinal Chemistry Inhibition of Apoptosis in Pediatric Cancer by Survivin
Current Pediatric Reviews Seeking the 5th Base of DNA Using Chromatographic Methods of Analysis
Current Organic Chemistry Tubulin-Targeting Agents in Hybrid Drugs
Current Medicinal Chemistry Gonadotropin-Releasing Hormone (GnRH) Receptors in Tumors: a New Rationale for the Therapeutical Application of GnRH Analogs in Cancer Patients?
Current Cancer Drug Targets Challenges in Managing Amniotic Fluid Embolism: An Up-to-Date Perspective on Diagnostic Testing with Focus on Novel Biomarkers and Avenues for Future Research
Current Pharmaceutical Biotechnology