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miR-573 is a negative regulator in the pathogenesis of rheumatoid arthritis

Cellular & Molecular Immunology volume 13, pages 839–849 (2016)Cite this article

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by abnormal inflammation, angiogenesis, and cartilage destruction. Our previous study demonstrated an increased expression of thioredoxin domain containing 5 (TXNDC5) in the synovial tissues of RA, and its overexpression was implicated in RA pathology. Although TXNDC5 variation is linked to genetic susceptibility to RA, the regulation of its abnormal expression has not been well defined. Here, we show that TXNDC5 is directly targeted by microRNA (miR)-573, and TXNDC5, in turn, mediates the suppressive effect of miR-573 on the invasion of synovial fibroblasts of RA (RASFs). miR-573 overexpression suppressed the expression of interleukin 6 (IL-6) and cyclooxygenase 2 in RASFs, as well as the production of tumor necrosis factor-alpha and interleukin-1 beta by activated THP-1 cells in response to lipopolysaccharide (LPS) stimulation. Moreover, treatment with conditioned medium of RASFs transfected with miR-573 mimic inhibited the angiogenic ability of human umbilical vein endothelial cells (HUVECs). Of note, epidermal growth factor receptor and Toll-like receptor 2 were validated as new direct targets of miR-573, and mediate the regulation of miR-573 on IL-6 production as well as the angiogenesis of HUVECs. In addition, exogenous miR-573 expression suppressed the activation of mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3, and phosphatidylinositol-3 kinase/activate protein kinase B in RASFs in response to LPS. Indeed, MAPK signaling was essential to ensure the function of miR-573. Taken together, our study points toward the protective roles of miR-573 in the pathological process of RA and suggests a potential target in the treatment of RA.

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Acknowledgements

This work was supported by a grant from the National Natural Science Foundation of China (Grant Nos. 81373218, 81302239, 81300426) and the Foundation for Scientific and Technological Achievements of Jinan (Grant No. 201302046).

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Author notes

  1. X Chang, Medical Research Center of Shandong Provincial Qianfoshan Hospital, Shandong University, Jingshi Road 16766, Jinan, Shandong 250014, People's Republic of China. E-mail: chang_qf@sina.com

Authors and Affiliations

  1. Research Center for Medicinal Biotechnology, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Shandong Academy of Medicinal Sciences, Jinan, People's Republic of China

    Lin Wang & Jihong Pan

  2. Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, People's Republic of China

    Guanhua Song

  3. Medical Research Center of Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, People's Republic of China

    Yabing Zheng & Xiaotian Chang

  4. Department of pathology, Linyi People's Hospital, Linyi, People's Republic of China

    Dan Wang & Hongyan Dong

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Supplementary Information accompanies the paper on Cellular & Molecular Immunology's website (http://www.nature.com/cmi).

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Wang, L., Song, G., Zheng, Y. et al. miR-573 is a negative regulator in the pathogenesis of rheumatoid arthritis. Cell Mol Immunol 13, 839–849 (2016). https://doi.org/10.1038/cmi.2015.63

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