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J Cell Mol Med. 2019 Apr;23(4):2702-2710. doi: 10.1111/jcmm.14175. Epub 2019 Feb 1.

Resveratrol promotes trophoblast invasion in pre-eclampsia by inducing epithelial-mesenchymal transition.

Author information

1
Department of Obstetrics and Gynecology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong Province, China.
2
Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
3
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale Stem Cell Center, Yale University School of Medicine, New Haven, Connecticut.
4
Department of Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China.
5
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
6
Department of General Surgery, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong Province, China.

Abstract

Impairment spiral arteries remodelling was considered to be the underlying cause of pathogenesis of pre-eclampsia (PE). Resveratrol (RE) was reported that it could modulate cellar phenotype to ameliorate diverse human diseases. However, the biological function of RE in PE remains poorly understood. In this report, we investigated the effect of RE on trophoblast phenotype both in vivo and in vitro. We conducted MTT and transwell assays to explore cell proliferation and invasion events in HTR-8/SVneo. In mice model, the clinical characteristics of PE were established through the injection of NG-nitro-l-arginine methyl ester (L-NAME). Furthermore, related experiments were performed to detect cellar phenotype-associated signalling pathway, including epithelial-mesenchymal transition (EMT) and Wnt/β-catenin. Cell assays indicated that RE could increase trophoblasts migration and invasion. In addition, hypertension and proteinuria were markedly ameliorated by RE compared with the controls in PE mice model. Moreover, treatment by RE in trophoblasts or in PE model, we found that RE activated EMT progress through the regulation of E-cadherin, β-catenin, N-cadherin, vimentin expression, and further altered the WNT-related gene expression, including WNT1, WNT3 and WNT5B. Our findings demonstrated that RE might stimulate the invasive capability of human trophoblasts by promoting EMT and mediating the Wnt/β-catenin pathway in PE.

KEYWORDS:

EMT; Wnt/β-catenin; pre-eclampsia; resveratrol; spiral artery remodelling

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