Abnormal DNA-binding of transcription factors in minimal change nephrotic syndrome
Abnormal DNA-binding of transcription factors in minimal change nephrotic syndrome
复制标题
微小病变肾病综合征中转录因子 DNA 结合异常
DOI：
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
Runmin Zhao
中科院分区：
文献类型：
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作者：
Changchun Cao;S. Lu;Chen Dong;Runmin Zhao
抽象的。核因子κB（NF-κB）和激活蛋白1（AP-1）等转录因子的激活在调节靶基因表达中起重要作用，包括参与微小病变型肾病综合征（MCNS）发病机制的细胞因子。糖皮质激素的治疗作用依赖于糖皮质激素受体（GR）作用于基因转录并与某些转录因子相互作用。为探讨转录因子在MCNS发病机制中的作用及糖皮质激素的治疗作用，我们采用电泳迁移率变动分析（EMSA）检测了6例MCNS患儿和6例健康对照者外周血单个核细胞（PBMC）中NF-κB、AP-1和GR的DNA结合能力。MCNS患者PBMC中NF-κB和AP-1的DNA结合能力在基线和佛波醇12-肉豆蔻酸酯13-乙酸酯（TPA）刺激后均显著高于对照组，但在地塞米松（DEX）治疗后下降至正常水平。GR DNA结合能力在基线和TPA治疗后显著降低，但DEX显著增强。尿蛋白定量与NF-κB、AP-1和GR的DNA结合能力呈显著正相关，提示NF-κB和AP-1的异常激活及GR DNA结合能力的降低可能参与了MCNS的发病过程。地塞米松抑制NF-κB和AP-1的表达及增强GR DNA结合能力可能是糖皮质激素对MCNS作用的分子基础。
Abstract. The activation of transcription factors such as nuclear factor κB (NF-κB) and activator protein 1 (AP-1) plays an important role in regulating the expression of target genes, including those for cytokines involved in pathogenesis of minimal change nephrotic syndrome (MCNS). The therapeutic effects of glucocorticoids depend on the glucocorticoid receptor (GR) acting on gene transcription and interacting with certain transcription factors. To explore the role of transcription factors in the pathogenesis of MCNS and the therapeutic effects of glucocorticoids, we examined the DNA-binding abilities of NF-κB, AP-1, and GR in peripheral blood mononuclear cells (PBMC) from 6 children with MCNS and 6 healthy controls by electrophoretic mobility shift assay (EMSA). NF-κB and AP-1 DNA-binding abilities were significantly increased both at baseline and after stimulation by phorbol 12-myristate 13-acetate (TPA) in PBMC from MCNS patients compared with controls, but declined to normal levels after treatment with dexamethasone (DEX). GR DNA-binding abilities were significantly reduced at baseline and after treatment with TPA, but were enhanced markedly by DEX. There were strong correlations between urinary protein and the baseline DNA binding ability of NF-κB or AP-1, or GR. These results suggested that the abnormal activation of NF-κB and AP-1 and the reduction of GR DNA-binding abilities may be involved in the pathogenesis of MCNS. Inhibition of NF-κB and AP-1 and enhancement of GR DNA-binding abilities by DEX may form the molecular basis of the effects of glucocorticoids in MCNS.
类固醇反应性肾病综合征中可溶性免疫反应抑制因子产生的调节系统。
影响因子：
19.6
作者：
Schnaper,HW
通讯作者：
Schnaper,HW