Blockade of translationally controlled tumor protein attenuated the aggressiveness of fibroblast-like synoviocytes and ameliorated collagen-induced arthritis
- 주제(기타) Biochemistry & Molecular Biology
- 주제(기타) Medicine, Research & Experimental
- 설명문(일반) [Kim, Mingyo; Choe, Yongho; Jeon, Min-Gyu; Park, Jin-Ho; Noh, Hae Sook; Cheon, Yun-Hong; Park, Hee Jin; Lee, Sang-Il] Gyeongsang Natl Univ, Sch Med & Hosp, Dept Internal Med, Jinju 52727, South Korea; [Kim, Mingyo; Choe, Yongho; Jeon, Min-Gyu; Park, Jin-Ho; Noh, Hae Sook; Cheon, Yun-Hong; Park, Hee Jin; Lee, Sang-Il] Gyeongsang Natl Univ, Sch Med & Hosp, Inst Hlth Sci, Jinju 52727, South Korea; [Lee, Heewon; Lee, Kyunglim] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea; [Park, Jaehun; Shin, Sung Jae] Yonsei Univ, Coll Med, Brain Korea 21 PLUS Project Med Sci, Dept Microbiol,Inst Immunol & Immunol Dis, Seoul 03722, South Korea
- 등재 SCIE, SCOPUS, KCI등재
- OA유형 gold, Green Published
- 발행기관 SPRINGERNATURE
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000175419
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/s12276-020-00546-y
- PubMed https://pubmed.ncbi.nlm.nih.gov/33408335
초록/요약
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, Behcet'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.
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