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

Authors
 Mingyo Kim  ;  Yongho Choe  ;  Heewon Lee  ;  Min-Gyu Jeon  ;  Jin-Ho Park  ;  Hae Sook Noh  ;  Yun-Hong Cheon  ;  Hee Jin Park  ;  Jaehun Park  ;  Sung Jae Shin  ;  Kyunglim Lee  ;  Sang-Il Lee 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.53(1) : 67-80, 2021-01 
Journal Title
EXPERIMENTAL AND MOLECULAR MEDICINE
ISSN
 1226-3613 
Issue Date
2021-01
MeSH
Animals ; Anti-Inflammatory Agents / pharmacology ; Anti-Inflammatory Agents / therapeutic use ; Arthritis, Experimental / drug therapy ; Arthritis, Experimental / metabolism* ; Arthritis, Rheumatoid / drug therapy ; Arthritis, Rheumatoid / metabolism* ; Cells, Cultured ; Fibroblasts / metabolism* ; Humans ; Mice ; Mice, Inbred C57BL ; Oligopeptides / pharmacology ; Oligopeptides / therapeutic use ; Protein Binding ; Synoviocytes / metabolism* ; Tumor Protein, Translationally-Controlled 1 / antagonists & inhibitors ; Tumor Protein, Translationally-Controlled 1 / genetics ; Tumor Protein, Translationally-Controlled 1 / metabolism*
Abstract
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.
DOI
10.1038/s12276-020-00546-y
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190343
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