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MicroRNA-21 in Scleroderma Fibrosis and its Function in TGF-β- Regulated Fibrosis-Related Genes Expression

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An Erratum to this article was published on 18 June 2013

Abstract

Uncontrolled fibrosis in multiple organs is the main cause of death in systemic sclerosis (SSc), and transforming growth factor-β (TGF-β) activation plays a fundamental role in the process. Our previous study demonstrated that miR-21 was significantly up-regulated in SSc fibroblasts. Here, we found that TGF-β regulated the expression of miR-21 and fibrosis-related genes, and decreased Smad7 expression. Over-expression of miR-21 in fibroblasts decreased the levels of Smad7, whereas knockdown of miR-21 increased its expression. Further study using a reporter gene assay demonstrated Smad7 was a direct target of miR-21. Similar to human SSc, the expression of miR-21 increased in the bleomycin induced skin fibrosis. Inhibition of fibrosis by treatment with anti-fibrosis drug bortezomib restored the levels of miR-21 and Smad7. MiR-21 may function in an amplifying circuit to enhance TGF-β signaling events in SSc fibrosis, and suggesting that miR-21 may act as a potential therapeutic target.

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Acknowledgments

This work was supported by grants from National Natural Science Foundation of China (30671947, 30900588), Fundamental Research Funds for the Central Universities (2012QNZT106), and Graduate Research Innovation Fund of Hunan Province (No. CX2011B061)

Conflict of interest statement

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of China

    Honglin Zhu, Hui Luo, Yisha Li, Yaou Zhou, Ying Jiang, Jin Chai, Yunhui You & Xiaoxia Zuo

  2. Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of China

    Xianzhong Xiao

Authors
  1. Honglin Zhu
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  2. Hui Luo
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  3. Yisha Li
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  4. Yaou Zhou
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  5. Ying Jiang
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  7. Xianzhong Xiao
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  8. Yunhui You
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Correspondence to Yunhui You or Xiaoxia Zuo.

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Honglin Zhu and Hui Luo contributed equally to this paper

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Zhu, H., Luo, H., Li, Y. et al. MicroRNA-21 in Scleroderma Fibrosis and its Function in TGF-β- Regulated Fibrosis-Related Genes Expression. J Clin Immunol 33, 1100–1109 (2013). https://doi.org/10.1007/s10875-013-9896-z

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  • DOI: https://doi.org/10.1007/s10875-013-9896-z

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