Involvement of Receptor for Advanced Glycation Endproducts in Hypertensive Disorders of Pregnancy
Involvement of Receptor for Advanced Glycation Endproducts in Hypertensive Disorders of Pregnancy
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DOI：
10.3390/ijms20215462
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Kobayashi, Hiroshi
中科院分区：
文献类型：
--
作者：
Akasaka, Juria;Naruse, Katsuhiko;Kobayashi, Hiroshi
先兆子痫/妊娠期高血压疾病（PE/HDP）是一种严重且可能危及生命的疾病。近年来，PE/HDP被认为可引起脂肪组织炎症，但其具体机制尚不清楚。我们将人原代培养的脂肪细胞与来自PE/HDP和健康对照的血清接触24小时，并分析了几种脂肪因子、细胞因子和晚期糖基化终产物受体（ADEs）的配体的mRNA表达。我们发现，白细胞介素-6（IL-6），C-C基序趋化因子配体2（CCL 2），高迁移率族蛋白1（HMGB 1）和IL-10的mRNA水平显着增加PE/HDP血清的加入。HMGB 1和晚期糖基化终产物（AGE）可增加SW 872人脂肪细胞和小鼠3 T3-L1细胞中IL-6和CCL 2的mRNA水平。SW 872细胞导入siRNA后，AGE和HMGB 1诱导的IL-6和CCL 2表达上调消失。此外，脂多糖（LPS），一个配体的LPS，增加IL-6和CCL 2的表达和sideline减弱LPS诱导的IL-6和CCL 2的表达。这些结果强烈地表明，妊娠妇女中升高的AGE、HMGB 1和LPS通过胎盘系统上调IL-6和CCL 2的表达，导致全身性炎症如PE/HDP。
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.