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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology*
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Movement / drug effects
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation / drug effects*
  • Humans
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Pre-Eclampsia / chemically induced
  • Pre-Eclampsia / drug therapy*
  • Pre-Eclampsia / genetics
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Resveratrol / pharmacology*
  • Trophoblasts / drug effects*
  • Trophoblasts / metabolism
  • Vimentin / genetics
  • Vimentin / metabolism
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway
  • beta Catenin

Substances

  • Antihypertensive Agents
  • CDH1 protein, rat
  • Cadherins
  • Ctnnb1 protein, rat
  • N-cadherin, rat
  • Nerve Tissue Proteins
  • Vimentin
  • Wnt Proteins
  • beta Catenin
  • Resveratrol
  • NG-Nitroarginine Methyl Ester