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The Lupus-derived Anti-double-stranded DNA IgG Contributes to Myofibroblast-like Phenotype in Mesangial Cells

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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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Abbreviations

BSA:

Bovine serum albumin

dsDNA:

Double-stranded DNA

ECM:

Extracellular matrix

ELISA:

Enzyme-linked immunosorbent assay

HAS:

Horse spleen apoferritin

LN:

Lupus nephritis

MC:

Mesangial cell

PBS:

Phosphate-buffered saline

PCR:

Polymerase chain reaction

SLE:

Systemic lupus erythematosus

SMA:

Smooth muscle actin

TGF:

Transforming growth factor

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Acknowledgements

This work was supported by a grant from National Natural Science Foundation of China (Project No.30972640, to CF and YX).

Conflict of interest statement

The authors declare that there are no competing interests.

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Authors and Affiliations

  1. Department of Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Yi Zhang, Layuan Xiong & Hong Cheng

  2. Department of Medicine, Gezhouba Central Hospital, The Third Clinical Hospital of Three Gorges University, Yichang, 443002, China

    Yi Zhang

  3. Department of Medicine, The First Affiliated Hospital of Yangtze University, Jingzhou, China

    Jiabin Yang

  4. Department of Dermatology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China

    Shan Jiang, Chunhong Fang & Yumin Xia

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  1. Yi Zhang
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  2. Jiabin Yang
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  5. Layuan Xiong
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Correspondence to Yumin Xia.

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Zhang, Y., Yang, J., Jiang, S. et al. The Lupus-derived Anti-double-stranded DNA IgG Contributes to Myofibroblast-like Phenotype in Mesangial Cells. J Clin Immunol 32, 1270–1278 (2012). https://doi.org/10.1007/s10875-012-9724-x

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  • DOI: https://doi.org/10.1007/s10875-012-9724-x

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