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Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive fibroblast-like synoviocytes (FLSs) and pannus formation. Various therapeutic strategies have been developed against inflammatory cytokines in RA in recent decades. Based on the migratory features of FLSs, we examined whe...

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Autores principales: Ji, Minjeong, Ryu, Hee Jung, Baek, Hyeon-Man, Shin, Dong Min, Hong, Jeong Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9076869/
https://www.ncbi.nlm.nih.gov/pubmed/35414711
http://dx.doi.org/10.1038/s12276-022-00756-6
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author Ji, Minjeong
Ryu, Hee Jung
Baek, Hyeon-Man
Shin, Dong Min
Hong, Jeong Hee
author_facet Ji, Minjeong
Ryu, Hee Jung
Baek, Hyeon-Man
Shin, Dong Min
Hong, Jeong Hee
author_sort Ji, Minjeong
collection PubMed
description Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive fibroblast-like synoviocytes (FLSs) and pannus formation. Various therapeutic strategies have been developed against inflammatory cytokines in RA in recent decades. Based on the migratory features of FLSs, we examined whether modulation of the migratory module attenuates RA severity. In this study, inflamed synovial fluid-stimulated FLSs exhibited enhanced migration and migratory apparatus expression, and sodium bicarbonate cotransporter n1 (NBCn1) was identified in primary cultured RA-FLSs for the first time. The NBC inhibitor S0859 attenuated the migration of FLSs induced with synovial fluid from patients with RA or with TNF-α stimulation. Inhibition of NBCs with S0859 in a collagen-induced arthritis (CIA) mouse model reduced joint swelling and destruction without blood, hepatic, or renal toxicity. Primary FLSs isolated from the CIA-induced mouse model also showed reduced migration in the presence of S0859. Our results suggest that inflammatory mediators in synovial fluid, including TNF-α, recruit NBCn1 to the plasma membrane of FLSs to provide dynamic properties and that modulation of NBCn1 could be developed into a therapeutic strategy for RA.
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spelling pubmed-90768692022-05-20 Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis Ji, Minjeong Ryu, Hee Jung Baek, Hyeon-Man Shin, Dong Min Hong, Jeong Hee Exp Mol Med Article Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive fibroblast-like synoviocytes (FLSs) and pannus formation. Various therapeutic strategies have been developed against inflammatory cytokines in RA in recent decades. Based on the migratory features of FLSs, we examined whether modulation of the migratory module attenuates RA severity. In this study, inflamed synovial fluid-stimulated FLSs exhibited enhanced migration and migratory apparatus expression, and sodium bicarbonate cotransporter n1 (NBCn1) was identified in primary cultured RA-FLSs for the first time. The NBC inhibitor S0859 attenuated the migration of FLSs induced with synovial fluid from patients with RA or with TNF-α stimulation. Inhibition of NBCs with S0859 in a collagen-induced arthritis (CIA) mouse model reduced joint swelling and destruction without blood, hepatic, or renal toxicity. Primary FLSs isolated from the CIA-induced mouse model also showed reduced migration in the presence of S0859. Our results suggest that inflammatory mediators in synovial fluid, including TNF-α, recruit NBCn1 to the plasma membrane of FLSs to provide dynamic properties and that modulation of NBCn1 could be developed into a therapeutic strategy for RA. Nature Publishing Group UK 2022-04-12 /pmc/articles/PMC9076869/ /pubmed/35414711 http://dx.doi.org/10.1038/s12276-022-00756-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ji, Minjeong
Ryu, Hee Jung
Baek, Hyeon-Man
Shin, Dong Min
Hong, Jeong Hee
Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis
title Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis
title_full Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis
title_fullStr Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis
title_full_unstemmed Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis
title_short Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis
title_sort dynamic synovial fibroblasts are modulated by nbcn1 as a potential target in rheumatoid arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9076869/
https://www.ncbi.nlm.nih.gov/pubmed/35414711
http://dx.doi.org/10.1038/s12276-022-00756-6
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