The Lupus-derived Anti-double-stranded DNA IgG Contributes to Myofibroblast-like Phenotype in Mesangial Cells |
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Authors: | Yi Zhang Jiabin Yang Shan Jiang Chunhong Fang Layuan Xiong Hong Cheng Yumin Xia |
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Affiliation: | 1. Department of Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China 2. Department of Medicine, Gezhouba Central Hospital, The Third Clinical Hospital of Three Gorges University, Yichang, 443002, China 3. Department of Medicine, The First Affiliated Hospital of Yangtze University, Jingzhou, China 4. Department of Dermatology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China
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Abstract: | 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. |
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