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Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment

Rheumatoid arthritis (RA) is a common autoimmune disease leading to pain, disability, and even death. Although studies have revealed that aberrant activation of STING was implicated in various autoimmune diseases, the role of STING in RA remains unclear. In the current study, we demonstrated that ST...

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Autores principales: Shen, Haotian, Jin, Lulu, Zheng, Qiangqiang, Ye, Ziqiang, Cheng, Linxiang, Wu, Yuxu, Wu, Honghao, Jon, Tae Gyong, Liu, Wenduo, Pan, Zongyou, Mao, Zhengwei, Wang, Yue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9761476/
https://www.ncbi.nlm.nih.gov/pubmed/36582350
http://dx.doi.org/10.1016/j.bioactmat.2022.12.001
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author Shen, Haotian
Jin, Lulu
Zheng, Qiangqiang
Ye, Ziqiang
Cheng, Linxiang
Wu, Yuxu
Wu, Honghao
Jon, Tae Gyong
Liu, Wenduo
Pan, Zongyou
Mao, Zhengwei
Wang, Yue
author_facet Shen, Haotian
Jin, Lulu
Zheng, Qiangqiang
Ye, Ziqiang
Cheng, Linxiang
Wu, Yuxu
Wu, Honghao
Jon, Tae Gyong
Liu, Wenduo
Pan, Zongyou
Mao, Zhengwei
Wang, Yue
author_sort Shen, Haotian
collection PubMed
description Rheumatoid arthritis (RA) is a common autoimmune disease leading to pain, disability, and even death. Although studies have revealed that aberrant activation of STING was implicated in various autoimmune diseases, the role of STING in RA remains unclear. In the current study, we demonstrated that STING activation was pivotal in RA pathogenesis. As the accumulation of dsDNA, a specific stimulus for STING, is a feature of RA, we developed a spherical polyethyleneimine-coated mesoporous polydopamine nanoparticles loaded with STING antagonist C-176 (PEI-PDA@C-176 NPs) for treating RA. The fabricated NPs with biocompatibility had high DNA adsorption ability and could effectively inhibit the STING pathway and inflammation in macrophages. Intra-articular administration of PEI-PDA@C-176 NPs could effectively reduce joint damage in mice models of dsDNA-induced arthritis and collagen-induced arthritis by inhibiting STING pathway. We concluded that materials with synergistic effects of STING inhibition might be an efficacious strategy to treat RA.
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spelling pubmed-97614762022-12-28 Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment Shen, Haotian Jin, Lulu Zheng, Qiangqiang Ye, Ziqiang Cheng, Linxiang Wu, Yuxu Wu, Honghao Jon, Tae Gyong Liu, Wenduo Pan, Zongyou Mao, Zhengwei Wang, Yue Bioact Mater Article Rheumatoid arthritis (RA) is a common autoimmune disease leading to pain, disability, and even death. Although studies have revealed that aberrant activation of STING was implicated in various autoimmune diseases, the role of STING in RA remains unclear. In the current study, we demonstrated that STING activation was pivotal in RA pathogenesis. As the accumulation of dsDNA, a specific stimulus for STING, is a feature of RA, we developed a spherical polyethyleneimine-coated mesoporous polydopamine nanoparticles loaded with STING antagonist C-176 (PEI-PDA@C-176 NPs) for treating RA. The fabricated NPs with biocompatibility had high DNA adsorption ability and could effectively inhibit the STING pathway and inflammation in macrophages. Intra-articular administration of PEI-PDA@C-176 NPs could effectively reduce joint damage in mice models of dsDNA-induced arthritis and collagen-induced arthritis by inhibiting STING pathway. We concluded that materials with synergistic effects of STING inhibition might be an efficacious strategy to treat RA. KeAi Publishing 2022-12-09 /pmc/articles/PMC9761476/ /pubmed/36582350 http://dx.doi.org/10.1016/j.bioactmat.2022.12.001 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Shen, Haotian
Jin, Lulu
Zheng, Qiangqiang
Ye, Ziqiang
Cheng, Linxiang
Wu, Yuxu
Wu, Honghao
Jon, Tae Gyong
Liu, Wenduo
Pan, Zongyou
Mao, Zhengwei
Wang, Yue
Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment
title Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment
title_full Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment
title_fullStr Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment
title_full_unstemmed Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment
title_short Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment
title_sort synergistically targeting synovium sting pathway for rheumatoid arthritis treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9761476/
https://www.ncbi.nlm.nih.gov/pubmed/36582350
http://dx.doi.org/10.1016/j.bioactmat.2022.12.001
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