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晚期糖基化终产物受体在妊娠期高血压疾病中的作用。

Involvement of Receptor for Advanced Glycation Endproducts in Hypertensive Disorders of Pregnancy.

机构信息

Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.

Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.

出版信息

Int J Mol Sci. 2019 Nov 1;20(21):5462. doi: 10.3390/ijms20215462.

DOI:10.3390/ijms20215462
PMID:31683992
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6862609/
Abstract

Preeclampsia/hypertensive disorders of pregnancy (PE/HDP) is a serious and potentially life-threatening disease. Recently, PE/HDP has been considered to cause adipose tissue inflammation, but the detailed mechanism remains unknown. We exposed human primary cultured adipocytes with serum from PE/HDP and healthy controls for 24 h, and analyzed mRNA expression of several adipokines, cytokines, and ligands of the receptor for advanced glycation endproducts (RAGE). We found that the mRNA levels of interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), high mobility group box 1 (HMGB1), and RAGE were significantly increased by the addition of PE/HDP serum. Among RAGE ligands, advanced glycation endproducts (AGE) and HMGB1 increased mRNA levels of IL-6 and CCL2 in SW872 human adipocytes and mouse 3T3-L1 cells. The introduction of small interfering RNA for RAGE (siRAGE) into SW872 cells abolished the AGE- and HMGB1-induced up-regulation of IL-6 and CCL2. In addition, lipopolysaccharide (LPS), a ligand of RAGE, increased the expression of IL-6 and CCL2 and siRAGE attenuated the LPS-induced expression of IL-6 and CCL2. These results strongly suggest that the elevated AGE, HMGB1, and LPS in pregnant women up-regulate the expression of IL-6 and CCL2 via the RAGE system, leading to systemic inflammation such as PE/HDP.

摘要

子痫前期/妊娠高血压疾病（PE/HDP）是一种严重且潜在威胁生命的疾病。最近，PE/HDP 被认为会引起脂肪组织炎症，但详细机制尚不清楚。我们将人原代培养的脂肪细胞与来自 PE/HDP 和健康对照组的血清共同孵育 24 小时，分析了几种脂肪因子、细胞因子和晚期糖基化终产物（RAGE）受体配体的 mRNA 表达。我们发现，PE/HDP 血清的加入显著增加了白细胞介素 6（IL-6）、C 型趋化因子配体 2（CCL2）、高迁移率族蛋白 1（HMGB1）和 RAGE 的 mRNA 水平。在 RAGE 配体中，晚期糖基化终产物（AGE）和 HMGB1 增加了 SW872 人脂肪细胞和小鼠 3T3-L1 细胞中 IL-6 和 CCL2 的 mRNA 水平。SW872 细胞中 RAGE 的小干扰 RNA（siRAGE）的引入消除了 AGE 和 HMGB1 诱导的 IL-6 和 CCL2 的上调。此外，RAGE 的配体脂多糖（LPS）增加了 IL-6 和 CCL2 的表达，siRAGE 减弱了 LPS 诱导的 IL-6 和 CCL2 的表达。这些结果强烈表明，孕妇体内升高的 AGE、HMGB1 和 LPS 通过 RAGE 系统上调 IL-6 和 CCL2 的表达，导致如 PE/HDP 等全身性炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1c5/6862609/b005fd2cd66b/ijms-20-05462-g009.jpg
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