17β-雌二醇对内皮细胞炎症相关微小RNA表达的影响

Effect of 17β-Estradiol on Endothelial Cell Expression of Inflammation- Related MicroRNA.

作者信息

Levy Ma'ayan V, Fandl Hannah K, Hijmans Jamie G, Stockelman Kelly A, Ruzzene Samuel T, Reiakvam Whitney R, Goldthwaite Zoe A, Greiner Jared J, DeSouza Christopher A, Garcia Vinicius P

机构信息

Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado Boulder Boulder, CO 80309, United States.

出版信息

Microrna. 2025;14(1):3-8. doi: 10.2174/0122115366320085240716180112.

DOI:10.2174/0122115366320085240716180112

PMID:39069709

Abstract

BACKGROUND

Estrogen plays a protective role in vascular health due, in part, to its regulation of endothelial inflammation. However, the mechanism(s) by which estrogen negatively regulates inflammatory signaling pathways is not completely understood. MicroRNAs (miRNAs) are recognized as sensitive and selective regulators of cardiovascular function, inflammation, and disease, yet the effects of 17β-estradiol on the endothelial miRNA profile are largely unknown.

OBJECTIVE

The aim of this study was to determine the effect of 17β-estradiol on the expression of inflammation-associated miRNAs in endothelial cells in vitro.

METHODS

Human Umbilical Vein Endothelial cells (HUVECs) were treated with media in the absence (control) and presence of 17β-estradiol (100 nM) for 24 hr. Thereafter, endothelial cell release of cytokines (IL-6 and IL-8), the intracellular expression of the central protein inflammatory mediator NF-κB, and the levels of inflammatory-associated miRNAs: miR-126, miR-146a, miR-181b, miR-204, and miR-Let-7a, were determined.

RESULTS

17β-estradiol-treated cells released significantly lower levels of IL-6 (47.6±1.5 pg/mL vs. 59.3±4.9 pg/mL) and IL-8 (36.3±2.3 pg/mL vs. 44.0±2.0 pg/mL). Cellular expression of total NF-κB (26.0±2.8 AU vs. 21.2±3.1 AU) was not different between groups; however, activated NF-κB (Ser536) (12.9±1.7 AU vs. 20.2±2.2 AU) was markedly reduced in 17β-estradiol-treated cells as compared to untreated cells. Furthermore, cellular expressions of miR-126 (1.8±0.3 fold), miR-146a (1.7±0.3 fold), miR-181b (2.1±0.4 fold), miR-204 (1.9±0.4 fold), and miR-Let-7a (1.8±0.3 fold) were markedly increased in response to 17β-estradiol treatment.

CONCLUSION

These data suggest that the anti-inflammatory effect of 17β-estradiol in endothelial cells may be mediated by miRNAs.

摘要

背景

雌激素在血管健康中发挥保护作用，部分原因在于其对内皮炎症的调节。然而，雌激素负向调节炎症信号通路的机制尚未完全明确。微小RNA（miRNA）被认为是心血管功能、炎症和疾病的敏感且具选择性的调节因子，但17β - 雌二醇对内皮miRNA谱的影响在很大程度上尚不清楚。

目的

本研究旨在确定17β - 雌二醇对体外培养的内皮细胞中炎症相关miRNA表达的影响。

方法

人脐静脉内皮细胞（HUVECs）在无（对照）和有17β - 雌二醇（100 nM）的培养基中处理24小时。此后，测定内皮细胞细胞因子（IL - 6和IL - 8）的释放、中心蛋白炎症介质NF - κB的细胞内表达以及炎症相关miRNA：miR - 126、miR - 146a、miR - 181b、miR - 204和miR - Let - 7a的水平。

结果

17β - 雌二醇处理的细胞释放的IL - 6（47.6±1.5 pg/mL对59.3±4.9 pg/mL）和IL - 8（36.3±2.3 pg/mL对44.0±2.0 pg/mL）水平显著降低。两组间总NF - κB的细胞表达（26.0±2.8 AU对21.2±3.1 AU）无差异；然而，与未处理细胞相比，17β - 雌二醇处理的细胞中活化的NF - κB（Ser536）（12.9±1.7 AU对20.2±2.2 AU）明显降低。此外，响应17β - 雌二醇处理，miR - 126（1.8±0.3倍）、miR - 146a（1.7±0.3倍）、miR - 181b（2.1±0.4倍）、miR - 204（1.9±0.4倍）和miR - Let - 7a（1.8±0.3倍）的细胞表达明显增加。