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作者

Mengsi Hu Yao Wang Yanping Meng Jinxiu Hu Jiao Qiao Junhui Zhen Decai Liang Minghua Fan

作者单位

Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China Contribution: Conceptualization (lead), Formal analysis (lead), Funding acquisition (lead), ​Investigation (lead), Methodology (lead), Project administration (equal), Writing - original draft (lead), Writing - review & editing (lead) Department of Obstetrics and Gynecology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China Contribution: Conceptualization (supporting), Formal analysis (supporting), ​Investigation (supporting), Methodology (supporting), Project administration (supporting), Resources (supporting), Software (supporting), Supervision (supporting), Writing - original draft (supporting), Writing - review & editing (supporting) Department of Obstetrics and Gynecology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China Contribution: Conceptualization (supporting), Formal analysis (supporting), ​Investigation (supporting), Methodology (supporting), Project administration (supporting), Supervision (supporting), Writing - original draft (supporting), Writing - review & editing (supporting) Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China Contribution: Formal analysis (supporting), ​Investigation (supporting), Methodology (supporting), Resources (supporting), Software (supporting) Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China Contribution: Formal analysis (supporting), ​Investigation (supporting), Resources (supporting), Validation (supporting) Department of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China Contribution: ​Investigation (supporting), Resources (supporting), Supervision (supporting) School of Statistics and Data Science, LPMC and KLMDASR, Nankai University, Tianjin, China Contribution: Formal analysis (supporting), Methodology (supporting), Resources (supporting) Department of Obstetrics and Gynecology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China Minghua Fan, Department of Obstetrics and Gynecology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. Contribution: Conceptualization (equal), Data curation (equal), Funding acquisition (equal), Methodology (equal), Project administration (equal), Resources (equal), Supervision (lead), Validation (equal), Writing - original draft (equal), Writing - review & editing (equal)

刊名

Journal of Cellular and Molecular Medicine

年份

2022

卷号

Vol.26 No.14

页码

4087-4100

关键词

H3K27me3 hypoxia nodal signalling placenta PRC2 preeclampsia trophoblast invasion TUG1

摘要

Inadequate trophoblastic invasion is considered as one of hallmarks of preeclampsia , which is characterized by newly onset of hypertension and proteinuria after 20 weeks of gestation. Accumulating evidence has indicated that long noncoding RNAs are aberrantly expressed in PE, whereas detailed mechanisms are unknown. In the present study, we showed that lncRNA Taurine upregulated 1 were downregulated in preeclamptic placenta and in HTR8/SVneo cells under hypoxic conditions, together with redu...更多

Inadequate trophoblastic invasion is considered as one of hallmarks of preeclampsia , which is characterized by newly onset of hypertension and proteinuria after 20 weeks of gestation. Accumulating evidence has indicated that long noncoding RNAs are aberrantly expressed in PE, whereas detailed mechanisms are unknown. In the present study, we showed that lncRNA Taurine upregulated 1 were downregulated in preeclamptic placenta and in HTR8/SVneo cells under hypoxic conditions, together with reduced enhancer of zeste homolog2 and embryonic ectoderm development expression, major components of polycomb repressive complex 2 , as well as activation of Nodal/ALK7 signalling pathway. Mechanistically, we found that TUG1 bound to PRC2 in HTR8/SVneo cells and weakened TUG1/PRC2 interplay was correlated with upregulation of Nodal expression via decreasing H3K27me3 mark at the promoter region of Nodal gene under hypoxic conditions. And activation of Nodal signalling prohibited trophoblast invasion via reducing MMP2 levels. Overexpression of TUG1 or EZH2 significantly attenuated hypoxia-induced reduction of trophoblastic invasiveness via negative modulating Nodal/ALK7 signalling and rescuing expression of its downstream target MMP2. These investigations might provide some evidence for novel mechanisms responsible for inadequate trophoblastic invasion and might shed some light on identifying future therapeutic targets for PE.收起

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