Details

Autor(en) / Beteiligte

• Kim, Mingyo
• Choe, Yongho
• Lee, Heewon
• Jeon, Min-Gyu
• Park, Jin-Ho
• Noh, Hae Sook
• Cheon, Yun-Hong
• Park, Hee Jin
• Park, Jaehun
• Shin, Sung Jae
• Lee, Kyunglim
• Lee, Sang-Il

Titel

Blockade of translationally controlled tumor protein attenuated the aggressiveness of fibroblast-like synoviocytes and ameliorated collagen-induced arthritis

Ist Teil von

• Experimental and Molecular Medicine, 2021, 53(0), , pp.1-14

Ort / Verlag

United States: Springer Nature B.V

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Histamine releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses, but the role of HRF/TCTP in rheumatoid arthritis (RA) remains undefined. In this study, we explored the pathogenic significance of HRF/TCTP and evaluated the therapeutic effects of HRF/TCTP blockade in RA. HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine the experimental phenotypes of RA. HRF/TCTP levels in the sera of RA patients were measured and compared to those from patients with osteoarthritis (OA), ankylosing spondylitis, Behçet's disease, and healthy controls. HRF/TCTP expression was also assessed in the synovium and fibroblast-like synoviocytes (FLSs) obtained from RA or OA patients. Finally, we assessed the effects of HRF/TCTP and dimerized HRF/TCTP-binding peptide-2 (dTBP2), an HRF/TCTP inhibitor, in RA-FLSs and CIA mice. Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were increased in HRF/TCTP TG mice and decreased in KD mice compared to wild-type littermates. HRF/TCTP levels in the sera, synovial fluid, synovium, and FLSs were higher in patients with RA than in control groups. Serum levels of HRF/TCTP correlated well with RA disease activity. The tumor-like aggressiveness of RA-FLSs was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice and had no detrimental effects in a murine tuberculosis model. Our results indicate that HRF/TCTP is a novel biomarker and therapeutic target for the diagnosis and treatment of RA.