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The Effect of SHH-Gli Signaling Pathway on the Synovial Fibroblast Proliferation in Rheumatoid Arthritis

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Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by chronic synovitis. This study aims to investigate the role of sonic hedgehog (SHH)-Gli signaling pathway in synovial fibroblast proliferation in rheumatoid arthritis. The expression of serum SHH in RA patients group was significantly increased compared with the systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and healthy subject (healthy control, HC) groups, respectively; serum SHH expression of RA patients was positively correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Ab), while there was no significant correlation between SHH expression and erythrocyte sedimentation rate (ESR). SHH, Ptch, Smo, and Gli molecules were highly expressed in rat RA-synovial fibroblast (RA-SF); after blocking the SHH-Gli signaling pathway with a Gli specific inhibitor, Gli-antagonist 61 (GANT61), RA-SF proliferation was inhibited in a dose-dependent manner and the apoptosis rate of RA-SF was increased as well; the expression levels of fibroblast growth factor receptor 1 (FGFR1) and FGFR3 declined in SF cells after GANT61 treatment. Our results suggest that SHH-Gli pathway is involved in the pathogenesis of RA, and blocking SHH-Gli pathway inhibits RA-SF cell proliferation and increases cell apoptosis, which may shed light on developing new ideas for RA treatment.

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Acknowledgements

This study was supported by the Superiority Discipline Project of Jiangsu University (2014); the Natural Science Foundation of the Jiangsu Higher Education Institutions (No15KJB310025); the Jiangsu Planned Projects for Postdoctoral Research Funds (No. 53470217); the Training Programs of Innovation and Entrepreneurship for College Students in Jiangsu Province (No. 201510313017Z); the Talents Scientific Research Foundation of Xuzhou Medical College (No. D2015004).

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    1. Department of pathogenic biology and Immunology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China

      Suping Qin, Hui Li, Xiangyang Li, Wei Pan, Chao Yan, Renxian Tang & Xiaomei Liu

    2. Department of Human Anatomy, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China

      Dexu Sun

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    1. Suping Qin
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    Correspondence to Renxian Tang or Xiaomei Liu.

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    Suping Qin and Dexu Sun contributed equally to this work.

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    Qin, S., Sun, D., Li, H. et al. The Effect of SHH-Gli Signaling Pathway on the Synovial Fibroblast Proliferation in Rheumatoid Arthritis. Inflammation 39, 503–512 (2016). https://doi.org/10.1007/s10753-015-0273-3

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