microRNA-520c-3p 通过下调 NLRP3 抑制子痫前期中 NLRP3 炎性小体的激活和炎症级联反应。

microRNA-520c-3p suppresses NLRP3 inflammasome activation and inflammatory cascade in preeclampsia by downregulating NLRP3.

机构信息

Obstetrics Department, The First Affiliated Hospital of the Medical College, Shihezi University, No. 107, North 2nd Road, Shihezi, 832008, The Xinjiang Uygur Autonomous Region, People's Republic of China.

出版信息

Inflamm Res. 2019 Aug;68(8):643-654. doi: 10.1007/s00011-019-01246-8. Epub 2019 May 30.

DOI:10.1007/s00011-019-01246-8

PMID:31143973

Abstract

BACKGROUND

The pathogenesis of preeclampsia (PE) is suggested to be a consequence of inflammation. Previously conducted investigations on nod-like receptor pyrin domain-containing 3 (NLRP3) have shed light to its crucial role in PE. Furthermore, microRNA-520c-3p (miR-520c-3p) is observed to be implicated in inflammation. Therefore, the current study aimed to explore the role of miR-520c-3p in inflammatory cascade of PE by targeting NLRP3.

METHODS

Microarray analyses were performed to screen differentially expressed genes associated with PE, and the potential relationship between miR-520c-3p and NLRP3 was analyzed. PE and normal placenta tissues were collected to determine the levels of inflammatory cytokines (IL-18, IL-33, IL-1β, IL-10, and TNF-α), miR-520c-3p and NLRP3. Hypoxic HTR8/SVneo cells were transfected with oe-NLRP3, si-NLRP3 or miR-520c-3p mimic to elucidate the functional role of NLRP3 or miR-520c-3p in the inflammatory cascade in PE, followed by the evaluation of levels of inflammatory cytokines and NLRP3 inflammasomes (NLRP3, ASC and caspase-1). Additionally, the HTR8/SVneo cell migration and invasion were evaluated.

RESULTS

An upregulation of NLRP3, IL-18, IL-1β and TNF-α, and downregulation of miR-520c-3p, IL-33 and IL-10 were observed in PE placenta tissues. NLRP3 was found to be a target gene of miR-520c-3p. HTR8/SVneo cells after hypoxia transfected with si-NLRP3 or miR-520c-3p mimic exhibited decreased levels of inflammatory cytokines and NLRP3 inflammasomes, in addition to increased IL-10 and IL-33 levels. Moreover, enhanced migration and invasion abilities were observed in cells transfected with si-NLRP3.

CONCLUSION

Collectively, miR-520c-3p could potentially inhibit NLRP3 inflammasome activation and inflammatory cascade in PE by downregulating NLRP3, highlighting the potential of miR-520c-3p as a therapeutic target for PE treatment.

摘要

背景

子痫前期（PE）的发病机制被认为是炎症的结果。先前对核苷酸结合寡聚结构域样受体含pyrin 结构域 3（NLRP3）的研究表明，其在 PE 中起关键作用。此外，miR-520c-3p 已被观察到与炎症有关。因此，本研究旨在通过靶向 NLRP3 来探讨 miR-520c-3p 在 PE 炎症级联中的作用。

方法

进行微阵列分析以筛选与 PE 相关的差异表达基因，并分析 miR-520c-3p 与 NLRP3 之间的潜在关系。收集 PE 和正常胎盘组织以确定炎症细胞因子（IL-18、IL-33、IL-1β、IL-10 和 TNF-α）、miR-520c-3p 和 NLRP3 的水平。用 oe-NLRP3、si-NLRP3 或 miR-520c-3p 模拟物转染缺氧 HTR8/SVneo 细胞，以阐明 NLRP3 或 miR-520c-3p 在 PE 炎症级联中的功能作用，然后评估炎症细胞因子和 NLRP3 炎性小体（NLRP3、ASC 和 caspase-1）的水平。此外，还评估了 HTR8/SVneo 细胞的迁移和侵袭能力。

结果

PE 胎盘组织中 NLRP3、IL-18、IL-1β 和 TNF-α 的表达上调，miR-520c-3p、IL-33 和 IL-10 的表达下调。NLRP3 是 miR-520c-3p 的靶基因。缺氧转染 si-NLRP3 或 miR-520c-3p 模拟物的 HTR8/SVneo 细胞炎症细胞因子和 NLRP3 炎性小体水平降低，IL-10 和 IL-33 水平升高。此外，转染 si-NLRP3 的细胞迁移和侵袭能力增强。