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

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.

Low-Dose Interleukin-2 Altered Gut Microbiota and Ameliorated Collagen-Induced Arthritis

“…On day 56, the mice were euthanized; their joints were fixed, embedded, and stained with hematoxylin and eosin. 39 , 40 …”

Role of Translationally Controlled Tumor Protein (TCTP) in the Development of Hypertension and Related Diseases in Mouse Models

“…Studies using genetically altered animal models, including conventional or tissue-specific TCTP-overexpressing and TCTP-deficient mice, have shed light on TCTP’s potential pathophysiological role in chronic diseases, such as osteoporosis [ 42 ], rheumatoid arthritis [ 43 ], and allergy [ 46 ]. Other studies have indicated the protective roles of TCTP due to its anti-apoptotic and cell-protective functions.…”

Role of TCTP in Cell Biological and Disease Processes

“…They generated a TCTP-overexpressing mouse and found that these display an improved metabolic homeostasis, with enhanced glucose tolerance, insulin sensitivity, and energy expenditure, compared to control mice [ 25 ]. In another paper, the group studied the importance of TCTP in rheumatoid arthritis (RA) [ 26 ]. They found that TCTP levels are increased in the sera and synovial fluids of patients with RA, compared to control groups.…”