PMID- 33408335 OWN - NLM STAT- MEDLINE DCOM- 20220215 LR - 20230127 IS - 2092-6413 (Electronic) IS - 1226-3613 (Print) IS - 1226-3613 (Linking) VI - 53 IP - 1 DP - 2021 Jan TI - Blockade of translationally controlled tumor protein attenuated the aggressiveness of fibroblast-like synoviocytes and ameliorated collagen-induced arthritis. PG - 67-80 LID - 10.1038/s12276-020-00546-y [doi] AB - 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. FAU - Kim, Mingyo AU - Kim M AD - Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Hospital, Jinju, 52727, Republic of Korea. FAU - Choe, Yongho AU - Choe Y AD - Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Hospital, Jinju, 52727, Republic of Korea. FAU - Lee, Heewon AU - Lee H AD - Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, 03760, Republic of Korea. FAU - Jeon, Min-Gyu AU - Jeon MG AD - Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Hospital, Jinju, 52727, Republic of Korea. FAU - Park, Jin-Ho AU - Park JH AD - Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Hospital, Jinju, 52727, Republic of Korea. FAU - Noh, Hae Sook AU - Noh HS AD - Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Hospital, Jinju, 52727, Republic of Korea. FAU - Cheon, Yun-Hong AU - Cheon YH AD - Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Hospital, Jinju, 52727, Republic of Korea. FAU - Park, Hee Jin AU - Park HJ AD - Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Hospital, Jinju, 52727, Republic of Korea. FAU - Park, Jaehun AU - Park J AD - Department of Microbiology, Institute for Immunology and Immunological Disease, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea. FAU - Shin, Sung Jae AU - Shin SJ AUID- ORCID: 0000-0003-0854-4582 AD - Department of Microbiology, Institute for Immunology and Immunological Disease, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea. FAU - Lee, Kyunglim AU - Lee K AD - Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, 03760, Republic of Korea. klyoon@ewha.ac.kr. FAU - Lee, Sang-Il AU - Lee SI AUID- ORCID: 0000-0002-8283-7001 AD - Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Hospital, Jinju, 52727, Republic of Korea. goldgu@gnu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210106 PL - United States TA - Exp Mol Med JT - Experimental & molecular medicine JID - 9607880 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Oligopeptides) RN - 0 (Tpt1 protein, mouse) RN - 0 (Tumor Protein, Translationally-Controlled 1) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology/therapeutic use MH - Arthritis, Experimental/drug therapy/*metabolism MH - Arthritis, Rheumatoid/drug therapy/*metabolism MH - Cells, Cultured MH - Fibroblasts/*metabolism MH - Humans MH - Mice MH - Mice, Inbred C57BL MH - Oligopeptides/pharmacology/therapeutic use MH - Protein Binding MH - Synoviocytes/*metabolism MH - Tumor Protein, Translationally-Controlled 1/antagonists & inhibitors/genetics/*metabolism PMC - PMC8080778 COIS- The authors declare that they have no conflict of interest. EDAT- 2021/01/08 06:00 MHDA- 2022/02/16 06:00 PMCR- 2021/01/06 CRDT- 2021/01/07 06:01 PHST- 2020/07/13 00:00 [received] PHST- 2020/11/05 00:00 [accepted] PHST- 2020/10/15 00:00 [revised] PHST- 2021/01/08 06:00 [pubmed] PHST- 2022/02/16 06:00 [medline] PHST- 2021/01/07 06:01 [entrez] PHST- 2021/01/06 00:00 [pmc-release] AID - 10.1038/s12276-020-00546-y [pii] AID - 546 [pii] AID - 10.1038/s12276-020-00546-y [doi] PST - ppublish SO - Exp Mol Med. 2021 Jan;53(1):67-80. doi: 10.1038/s12276-020-00546-y. Epub 2021 Jan 6.