MicroRNA miR-27a as a possible regulator of anti-inflammatory macrophage phenotype in preeclamptic placenta

Placenta. 2024. Vol. 145. P. 151–161.

Vishnyakova P., Gantsova E., Kiseleva V., Lazarev D., Князев Е. Н., Poltavets A., Iskusnykh M., Muminova K., Potapova A., Khodzhayeva Z., Elchaninov A., Fatkhudinov T., Sukhikh G.

Introduction

The role of the TGFβ signaling pathway, an important cascade responsible for the anti-inflammatory polarization of macrophages, in the development of both early- and late-onset preeclampsia (eoPE and loPE), remains poorly understood. In this study, we examined the components of the TGFβ signaling cascade and macrophage markers within placental tissue in normal pregnancy and in PE.

Methods

Patients with eoPE, loPE, and normal pregnancy were enrolled in the study (n = 10 in each group). The following techniques were used for the investigation: immunohistochemistry analysis, western blotting, qRT-PCR, isolation of monocytes by magnetic sorting, transfection, microRNA sequencing, and bioinformatic analysis.

Results

We observed a significant decrease in the anti-inflammatory macrophage marker CD206 in the loPE group, alongside with a significant down-regulation of CD206 protein production in both eoPE and loPE groups. The level of CD68-positive cells and relative levels of CD163 and MARCO production were comparable across the groups. However, we identified a significant decrease in the TGFβ receptor 2 production and its gene expression in the PE group. Further analysis revealed a link between TGFBR2 and MRC1 (CD206) genes through a single miRNA, hsa-miR-27a-3p. Transfecting CD14-derived macrophages with the hsa-miR-27a-3p mimic significantly changed TGFBR2 production, indicating the potential role of this miRNA in regulating the TGFβ signaling pathway. We also revealed the up-regulation of hsa-miR-27a-5p and hsa-miR-27a-3p in the trophoblast BeWo b30 cell line under the severe hypoxia condition and the fact that TGFBR2 3′ UTR could serve as a potential target for these miRNAs.

Discussion

Our findings uncover a novel potential therapeutic target for managing patients with PE, significantly contributing to a deeper comprehension of the underlying mechanisms involved in the development of this pathology.

Ключевые слова: микроРНК, microRNA, гипоксия, Preeclampsia, Преэклампсия, hypoxia, макрофаги, TGF beta, TGFβ, TGFβ receptor 1, Macrophages, CD206, miR-27a, ТФР бета, ТФРβ, Рецептор ТФРβ, CD206, miR-27a

ПУБЛИКАЦИЯ ПОДГОТОВЛЕНА ПО РЕЗУЛЬТАТАМ ПРОЕКТА: Роль молекул микроРНК в противоопухолевом и противовирусном иммунитете (2023)