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Decreased expression of JHDMID in placenta is associated with preeclampsia through HLA-G

Journal of Human Hypertension volume 32, pages 448–454 (2018)Cite this article

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Abstract

The exact mechanism of preeclampsia (PE) remains unclear, accumulating researches have indicated multiple epigenetic factors relate to PE and histone methylation plays a crucial role in modifying the gene expression. So we aimed to confirm that abnormal expression of histone demethylase JHDM1D contributes to PE and lower expression of HLA-G in PE. We tested the expression of JHDM1D, H3K9me2, and H3K27me2 in the placentas of PE and normal control (NC)women who had a healthy pregnancy with Immunohistochemistry and we found that JHDM1D, H3K9me2, and H3K27me2 were all mainly expressed in the nuclei of the extra-villous trophoblasts (EVTs). JHDM1D was lower expressed in PE than in NC placentas, corresponding with the mRNA level and protein level with qTR-PCR and western blot, while H3K9me2 and H3K27me2 were higher expressed in PE. We further investigated the biological functions of JHDM1D in HTR-8/SVneo cells. We found that siJHDM1D inhibited cell growth after 24 h of the transfection and reduced the invasion, while increasing the apoptosis of HTR-8/SVneo. We then constructed the siJHDM1D stable cell line and confirmed with CHIP-qPCR that siJHDM1D inhibited the expression of HLA-G through increased the enrichment of H3K9me2 and H3K27me2 in the JHDM1D bounding region of HLA-G. Taken together, our study confirms that decreased expression of JHDM1D is associated with PE through down-regulating HLA-G and casts new light to the diagnosis and therapy of PE.

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Funding

This work was supported by National Key R&D Program of China (2016YFC1000403) and by Natural Science Foundation of China (Grant No. 81471470 to W.-R.G.).

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  1. These authors contributed equally: Shouling Luo, Jiangnan Pei.

Authors and Affiliations

  1. The Department of Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China

    Shouling Luo, Jiangnan Pei, Xiaotian Li & Weirong Gu

  2. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China

    Shouling Luo & Jiangnan Pei

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  1. Shouling Luo
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  2. Jiangnan Pei
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Correspondence to Weirong Gu.

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Luo, S., Pei, J., Li, X. et al. Decreased expression of JHDMID in placenta is associated with preeclampsia through HLA-G. J Hum Hypertens 32, 448–454 (2018). https://doi.org/10.1038/s41371-018-0062-1

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