Department of Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
J Clin Immunol. 2012 Dec;32(6):1270-8. doi: 10.1007/s10875-012-9724-x. Epub 2012 Jun 24.
Anti-double-stranded DNA (dsDNA) antibodies have been indicated to play a major role in the pathogenesis of lupus nephritis (LN), which is characterized by mesangial alterations, including phenotypic changes. To explore the effects of anti-dsDNA antibodies on the phenotype of mesangial cells (MCs), the anti-dsDNA IgG in sera and histological features of glomeruli were analyzed in the mice models of immune-complex glomerulonephritis. The MCs were cultured in vitro with the addition of anti-dsDNA or non-anti-dsDNA IgG. Compared to the anti-dsDNA-negative controls, the serum positive mice had increased extracellular matrix accumulation and higher alpha-smooth muscle actin expression in the mesangial region. The anti-dsDNA IgG enhanced the synthesis of transforming growth factor beta, alpha-smooth muscle actin, and fibronectin, and even induced the myofibroblast-like morphological features in cultured MCs. Our results indicated that anti-dsDNA antibodies contribute to the phenotypic changes in MCs, which suggests another mechanism of renal injuries in LN induced by anti-dsDNA antibodies.
抗双链 DNA（dsDNA）抗体在狼疮肾炎（LN）的发病机制中起着重要作用，其特征为系膜改变，包括表型变化。为了探讨抗 dsDNA 抗体对系膜细胞（MC）表型的影响，分析了免疫复合物性肾小球肾炎小鼠模型中的血清抗 dsDNA IgG 和肾小球的组织学特征。将 MC 在体外与抗 dsDNA 或非抗 dsDNA IgG 共培养。与抗 dsDNA 阴性对照相比，血清阳性小鼠的细胞外基质积累增加，系膜区的α-平滑肌肌动蛋白表达升高。抗 dsDNA IgG 增强了转化生长因子β、α-平滑肌肌动蛋白和纤维连接蛋白的合成，甚至在培养的 MC 中诱导出肌成纤维细胞样形态特征。我们的结果表明，抗 dsDNA 抗体有助于 MC 的表型变化，这提示了抗 dsDNA 抗体诱导的 LN 肾损伤的另一种机制。
