Aspirin facilitates trophoblast invasion and epithelial-mesenchymal transition by regulating the miR-200-ZEB1 axis in preeclampsia

Mei Tsz Su, Pei Yin Tsai, Chia Yih Wang, Hui Ling Tsai, Pao Lin Kuo

Research output: Contribution to journalArticlepeer-review

Abstract

Preeclampsia is a severe gestational hypertensive disorder that occurs after 20 weeks’ of gestation. It involves several maternal systems, such as cardiovascular, renal, coagulatory systems, and poses a major threat to the maternal and fetal health. Recent clinical evidence showed that aspirin is an effective preventative treatment for reducing the incidence of premature preeclampsia among high-risk pregnant women, however, the mechanism of drug action is not clear. miR-200 family has been shown to be associated with preeclampsia and upregulated in the plasma and placenta of preeclamptic patients. Here we revealed that miR-200 family inhibited trophoblast invasion and epithelial-mesenchymal transition (EMT) process by stimulating epithelial marker expression (E-cadherin and ZO-1) and repressing mesenchymal marker expression (ZEB1 and TGFβ1). Similarly, EMT markers in the placenta of preeclamptic patients showed higher E-cadherin and lower ZEB1 and TGF-β1 protein expression. Moreover, aspirin was shown to suppress miR-200 family and these miR-200 family-mediated cell functions, including cell invasion and EMT changes, were completely reversed. In conclusion, this study demonstrates the effect of miR-200 family on trophoblast invasion and EMT. For the first time, aspirin was shown to fully reverse miR-200-mediated trophoblast biology and act through the network signaling of TGF-β1/ZEB1/miR-200. These results provide a plausible mechanism explaining aspirin's effect on preeclampsia prevention and a therapeutic target for disease intervention.

Original languageEnglish
Article number111591
JournalBiomedicine and Pharmacotherapy
Volume139
DOIs
Publication statusPublished - 2021 Jul

All Science Journal Classification (ASJC) codes

  • Pharmacology

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