机构：[1]Department of Rheumatology and Immunology, the Second Affiliated Hospital of Soochow University, Suzhou[2]Department of Biological Science & Engineering, Hebei University of Science & Technology, Hebei, China
Objectives. Oestrogens have been shown to play key roles in the pathogenesis of SLE. The aim of this study was to investigate the roles and mechanisms of 17 beta-estradiol (E2) in TNF-like weak inducer of apoptosis (TWEAK) expression in LN. Methods. Peripheral blood mononuclear cells (PBMCs) obtained from LN patients were used for in vitro experiments, while female MRL/lpr and MRL/MpJ mice were used for in vivo studies. E2, ICI 182 780 [estrogen receptor (ER)-selective antagonist], methyl-piperidino-pyrazole (MPP, ER alpha-selective modulator), lentivirus (LV)-TWEAK-short hairpin RNA (shRNA) and LV-control-shRNA treatments were used in this study. Results. TWEAK mRNA expression in PBMCs was significantly increased following E2 treatment and downregulated after incubation with ICI 182 780 or MPP. Compared with sham-operated MRL/lpr mice, ovariectomized mice, treated with dimethyl sulphoxide vehicle alone, showed lower expression levels of renal TWEAK mRNA and protein. The expression of both mRNA and protein in ovariectomized mice was upregulated after E2 treatment and downregulated after ICI 182 780 or MPP co-treatment. Severe renal damage was observed in E2-treated ovariectomized mice, as were higher serum levels of IL-6, compared with dimethyl sulphoxide vehicle-treated ovariectomized mice. Co-treatment with LV-TWEAK-shRNA reversed these changes, and LV-control-shRNA treatment had no effect on them. Conclusion. Our results demonstrated that E2 plays an important role in the upregulation of TWEAK expression in LN, most likely through an ER alpha-dependent pathway, causing kidney damage. This provides a novel insight into the mechanisms of the E2-TWEAK signalling pathway in LN.
基金：
This work was partially supported by the Suzhou
Science and Technology Development Project (Grant No.
SYS201231) and the National Natural Science Foundation
of China (Grant No. 81200507).
第一作者机构：[1]Department of Rheumatology and Immunology, the Second Affiliated Hospital of Soochow University, Suzhou
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Rheumatology and Immunology, the Second Affiliated Hospital of Soochow University, Sanxiang Road No.1055, Suzhou, Jiangsu, 215000, P. R. China.
推荐引用方式(GB/T 7714)：
Leixi Xue,Zhiqin Liu,Ji Hu,et al.Estrogen-induced expression of tumor necrosis factor-like weak inducer of apoptosis through ER alpha accelerates the progression of lupus nephritis[J].RHEUMATOLOGY.2016,55(10):1880-8.doi:10.1093/rheumatology/kew248.
APA：
Leixi Xue,Zhiqin Liu,Ji Hu,Jun Huang,Jian Wen&Zhichun Liu.(2016).Estrogen-induced expression of tumor necrosis factor-like weak inducer of apoptosis through ER alpha accelerates the progression of lupus nephritis.RHEUMATOLOGY,55,(10)
MLA：
Leixi Xue,et al."Estrogen-induced expression of tumor necrosis factor-like weak inducer of apoptosis through ER alpha accelerates the progression of lupus nephritis".RHEUMATOLOGY 55..10(2016):1880-8
医学