Format

Send to

Choose Destination
Hypertension. 2017 Feb;69(2):356-366. doi: 10.1161/HYPERTENSIONAHA.116.08483. Epub 2017 Jan 3.

Dysregulated DNA Methyltransferase 3A Upregulates IGFBP5 to Suppress Trophoblast Cell Migration and Invasion in Preeclampsia.

Author information

1
From the Clinical and Translational Research Center (Y.J., X.H., X.X., X.Z., L. Jia, J. Zhu, D.X., K.W., Q.Z., L. Jin) and Department of Obstetrics (T.L., T.D.), Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, China; and Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (J. Zhang).
2
From the Clinical and Translational Research Center (Y.J., X.H., X.X., X.Z., L. Jia, J. Zhu, D.X., K.W., Q.Z., L. Jin) and Department of Obstetrics (T.L., T.D.), Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, China; and Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (J. Zhang). jqzhang@bio.ecnu.edu.cn tduan@yahoo.com.

Abstract

Preeclampsia is a unique multiple system disorder during human pregnancy, which affects ≈5% to 8% of pregnancies. Its risks and complications have become the major causes of maternal and fetal morbidity and mortality. Although abnormal placentation to which DNA methylation dysregulation is always linked is speculated to be one of the reasons causing preeclampsia, the underlying mechanisms still remain elusive to date. Here we revealed that aberrant DNA methyltransferase 3A (DNMT3A) plays a critical role in preeclampsia. Our results show that the expression and localization of DNMT3A are dysregulated in preeclamptic placenta. Moreover, knockdown of DNMT3A obviously inhibits trophoblast cell migration and invasion. Mechanistically, IGFBP5 (insulin-like growth factor-binding protein 5), known as a suppressor, is upregulated by decreased DNMT3A because of promoter hypomethylation. Importantly, IGFBP5 downregulation can rescue the defects caused by DNMT3A knockdown, thereby, consolidating the significance of IGFBP5 in the downstream of DNMT3A in trophoblast. Furthermore, we detected low promoter methylation and high protein expression of IGFBP5 in the clinical samples of preeclamptic placenta. Collectively, our study suggests that dysregulation of DNMT3A and IGFBP5 is relevant to preeclampsia. Thus, we propose that DNMT3A and IGFBP5 can serve as potential markers and targets for the clinical diagnosis and therapy of preeclampsia.

KEYWORDS:

DNA methylation; DNMT3A; IGFBP5; migration and invasion; preeclampsia; trophoblast

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center