Puerarin attenuates preeclampsia-induced trophoblast mobility loss and inflammation by modulating miR-181b-5p/RBAK axis.

Abstract

Preeclampsia (PE) is a serious pregnancy complication characterized by inflammation and impaired trophoblast motility. Puerarin (Pue) is a functional compound with anti-PE potential. The current study aimed to explore the therapeutic effects of Pue on PE as well as the associated mechanism by focusing on the interaction between Pue and microRNAs (miRs). Human villous trophoblast HTR-8/SVneo cells were treated with TNF-α and Pue, and a change in miR expression profile was determined. The anti-PE effects of Pue were validated in rat models by measuring blood pressure, 24-h proteinuria, and cytokine levels. The mechanism was explored by focusing on miR-181b-5p/RBAK axis. The induction of PE increased blood pressure and 24-h proteinuria, and induced TNF-α, IL-1β, and IL-6 levels, which was reversed by Pue. In in vitro assays, TNF-α suppressed viability, induced apoptosis and inflammatory response, and inhibited migration in trophoblasts, which was attenuated by Pue. At molecular level, the expression level of miR-181b-5p was both induced in vivo and in vitro with the development of PE symptoms, contributing to the inhibited expression of RBAK. The induced expression of miR-181b-5p under Pue treatment showed that the reinduction of miR-181b-5p counteracted the effects of Pue, indicating the key role of the miR in the protective effects of Pue against PE. The current study verified the anti-PE function of Pue: the compound suppressed inflammatory response associated with PE, and improved trophoblast motility. The effects depended on the inhibition of miR-181b-5p that inhibited the expression of RBAK.