Resveratrol promotes trophoblast invasion in pre-eclampsia by inducing epithelial-mesenchymal transition
Resveratrol promotes trophoblast invasion in pre-eclampsia by inducing epithelial-mesenchymal transition
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白藜芦醇通过诱导上皮间质转化促进先兆子痫的滋养层侵袭
DOI：
10.1111/jcmm.14175
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发表时间：
2019
影响因子：
5.3
通讯作者：
Sun Lizhou
中科院分区：
文献类型：
--
作者：
Zou Yanfen;Li Shuhong;Wu Dan;Xu Yetao;Wang Sailan;Jiang Ying;Liu Fang;Jiang Ziyan;Qu Hongmei;Yu Xiang;Wang Xiaoli;Wang Yuanli;Sun Lizhou
螺旋动脉重塑受损被认为是先兆子痫（PE）发病机制的根本原因。白藜芦醇（resveratrol，RE）是近年来发现的一种具有调节细胞表型作用的物质，可用于多种疾病的治疗.然而，RE在PE中的生物学功能仍然知之甚少。在这份报告中，我们研究了RE在体内和体外对滋养层细胞表型的影响。我们进行了MTT和transwell测定以探索HTR-8/SVneo中的细胞增殖和侵袭事件。在小鼠模型中，通过注射NG-硝基-L-精氨酸甲酯（L-NAME）建立PE的临床特征。此外，进行相关实验以检测细胞表型相关信号通路，包括上皮-间质转化（EMT）和Wnt/β-catenin。细胞实验表明RE可增加滋养细胞的迁移和侵袭。此外，RE对PE小鼠模型的高血压和蛋白尿也有明显的改善作用。此外，在滋养层细胞或PE模型中，我们发现RE通过调节E-cadherin，β-catenin，N-cadherin，vimentin的表达激活EMT进展，并进一步改变WNT相关基因的表达，包括WNT 1，WNT 3和WNT 5 B。我们的研究结果表明，RE可能通过促进EMT和介导PE中的Wnt/β-catenin通路来刺激人滋养层细胞的侵袭能力。
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.