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MiR-130a/Ndrg2 Axis Inhibits the Proliferation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

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Abstract

Studies have found that N-myc downstream–regulated gene 2 (Ndrg2) is involved in the progression of rheumatoid arthritis (RA); however, the specific mechanism still remains unclear. Gene expression profiles in the tibial joints of the collagen-induced rheumatoid arthritis model were obtained using Gene Expression Omnibus database. Western blot and real-time PCR were respectively performed to determine the expression of Ndrg2 and gene messenger RNA. Cell viability was measured by Cell Counting Kit-8 (CCK-8) method, and cell cycle was detected by flow cytometry. Cell scratch assays were carried out to detect migration. The binding ability of miR-130a to Ndrg2-3′-UTR was predicted by TargetScan website and confirmed by dual luciferase assay. A collagen-induced arthritis rat model was constructed to observe the effects of miR-130a on arthritis index, hind limb swelling, volume of rat hind paw, and inflammation. Ndrg2 was found downregulated in RA tissues, and knockdown of Ndrg2 promoted fibroblast-like synoviocytes (FLS) proliferation and inflammation, while overexpressed Ndrg2 produced opposite results. Ndrg2 was predicted as a target gene for miR-130a, and miR-130a mimic promoted FLS proliferation, while miR-130a inhibitor suppressed FLS proliferation. Moreover, we found that miR-130a antagomir could significantly reduce the arthritis index, swelling degree, foot volume, and inflammatory factor levels; inhibit the expression of miR-130a; and promote the expression of Ndrg2. The miR-130a/Ndrg2 axis signaling pathway is involved in the progression of RA. Our findings provide a theoretical basis for the clinical treatment of RA.

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Authors and Affiliations

  1. Department of Rheumatology, Gansu Provincial Hospital of Traditional Chinese Medicine, No. 418, Guazhou Road, Qilihe District, Lanzhou City, 730050, Gansu Province, China

    Xiaojun Su & Haidong Wang

  2. Department of Acupuncture and Moxibustion, Gansu Provincial Hospital of Traditional Chinese Medicine, No. 418, Guazhou Road, Qilihe District, Lanzhou City, 730050, Gansu Province, China

    Hongtao Zhang

  3. Department of Orthopedics, Qilu Hospital of Shandong University, No. 107, West Wenhua Road, Jinan City, 250012, Shandong Province, China

    Pengfei Sun

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Su, X., Zhang, H., Wang, H. et al. MiR-130a/Ndrg2 Axis Inhibits the Proliferation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis. Inflammation 43, 2048–2060 (2020). https://doi.org/10.1007/s10753-019-01118-7

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