Decreased Expression and Altered Methylation of Syncytin-1 Gene in Human Placentas Associated with Preeclampsia

被引:68
作者
Zhuang, Xue-Wei [1 ,2 ]
Li, Jinping [2 ,3 ,4 ]
Brost, Brian C. [3 ,4 ]
Xia, Xi-Yan [2 ,5 ]
Chen, Hai Bin [6 ]
Wang, Chuan-Xin [1 ]
Jiang, Shi-Wen [2 ,3 ,4 ,7 ]
机构
[1] Shandong Univ, QiLu Hosp, Dept Clin Lab, Jinan 250100, Peoples R China
[2] Mercer Univ, Sch Med, Dept Biomed Sci, Savannah, GA 31404 USA
[3] Mayo Clin, Dept Obstet & Gynecol, Rochester, MN 55905 USA
[4] Mayo Med Coll, Rochester, MN 55905 USA
[5] Jinan Nursing Coll, Dept Immunol, Jinan, Peoples R China
[6] Shantou Univ, Med Coll Shantou, Shantou, Guangdong, Peoples R China
[7] Mem Univ Med Ctr, Dept Obstet & Gynecol, Savannah, GA 31404 USA
关键词
Syncytin-1; DNA methylation; preeclampsia; trophoblast; placenta; DNA METHYLATION; TROPHOBLAST; CANCER; FUSION; SYSTEM;
D O I
10.2174/13816128113199990541
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:1796 / 1802
页数:7
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