MiR-130a/Ndrg2 Axis Inhibits the Proliferation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis
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ORIGINAL ARTICLE
MiR-130a/Ndrg2 Axis Inhibits the Proliferation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis Xiaojun Su,1 Hongtao Zhang,2 Haidong Wang,1 and Pengfei Sun
3,4
Received 10 July 2019; accepted 10 October 2019
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. Abstract—
KEY WORDS: rheumatoid arthritis; Ndrg2; miR-130a; proliferation; inflammation.
INTRODUCTION 1
Department of Rheumatology, Gansu Provincial Hospital of Traditional Chinese Medicine, No. 418, Guazhou Road, Qilihe District, Lanzhou City, 730050, Gansu Province, China 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 3 Department of Orthopedics, Qilu Hospital of Shandong University, No. 107, West Wenhua Road, Jinan City, 250012, Shandong Province, China 4 To whom correspondence should be addressed at Department of Rheumatology, Gansu Provincial Hospital of Traditional Chinese Medicine, No. 418, Guazhou Road, Qilihe District, Lanzhou City, 730050, Gansu Province, China. E-mail: [email protected]
As a chronic systemic autoimmune disease, rheumatoid arthritis (RA) is characterized by joint synovial inflammation; however, its pathogenesis and specific etiology have not yet been fully clarified [5]. The average incidence of RA in the world is about 1%, while that in China accounts for 0.3~0.4% [18]. Synovial inflammati
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