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

葛根素 子痫前期 滋养层 炎症 细胞凋亡 肿瘤坏死因子α 下调和上调 化学 促炎细胞因子 男科 体内 药理学 内分泌学 医学 内科学 免疫学 生物 怀孕 生物化学 胎盘 胎儿 病理 基因 替代医学 生物技术 遗传学
作者
Jinjuan Guo,Weiqiao Bian,Huadong Jiang
出处
期刊:American Journal of Reproductive Immunology [Wiley]
卷期号:87 (2) 被引量:10
标识
DOI:10.1111/aji.13510
摘要

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.
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