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Role of Endoplasmic Reticulum Stress in Rheumatoid Arthritis Pathogenesis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by abnormal proliferation of synoviocytes, leukocyte infiltration, and angiogenesis. The endoplasmic reticulum (ER) is the site of biosynthesis for all secreted and membrane proteins. The accumulation of unfolded proteins in t...

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Autores principales: Park, Yune-Jung, Yoo, Seung-Ah, Kim, Wan-Uk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Academy of Medical Sciences 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890471/
https://www.ncbi.nlm.nih.gov/pubmed/24431899
http://dx.doi.org/10.3346/jkms.2014.29.1.2
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author Park, Yune-Jung
Yoo, Seung-Ah
Kim, Wan-Uk
author_facet Park, Yune-Jung
Yoo, Seung-Ah
Kim, Wan-Uk
author_sort Park, Yune-Jung
collection PubMed
description Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by abnormal proliferation of synoviocytes, leukocyte infiltration, and angiogenesis. The endoplasmic reticulum (ER) is the site of biosynthesis for all secreted and membrane proteins. The accumulation of unfolded proteins in the ER leads to a condition known as ER stress. Failure of the ER's adaptive capacity results in abnormal activation of the unfolded protein response. Recently, we have demonstrated that ER stress-associated gene signatures are highly expressed in RA synovium and synovial cells. Mice with Grp78 haploinsufficiency exhibit the suppression of experimentally induced arthritis, suggesting that the ER chaperone GRP78 is crucial for RA pathogenesis. Moreover, increasing evidence has suggested that GRP78 participates in antibody generation, T cell proliferation, and pro-inflammatory cytokine production, and is therefore one of the potential therapeutic targets for RA. In this review, we discuss the putative, pathophysiological roles of ER stress and GRP78 in RA pathogenesis.
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spelling pubmed-38904712014-01-15 Role of Endoplasmic Reticulum Stress in Rheumatoid Arthritis Pathogenesis Park, Yune-Jung Yoo, Seung-Ah Kim, Wan-Uk J Korean Med Sci Review Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by abnormal proliferation of synoviocytes, leukocyte infiltration, and angiogenesis. The endoplasmic reticulum (ER) is the site of biosynthesis for all secreted and membrane proteins. The accumulation of unfolded proteins in the ER leads to a condition known as ER stress. Failure of the ER's adaptive capacity results in abnormal activation of the unfolded protein response. Recently, we have demonstrated that ER stress-associated gene signatures are highly expressed in RA synovium and synovial cells. Mice with Grp78 haploinsufficiency exhibit the suppression of experimentally induced arthritis, suggesting that the ER chaperone GRP78 is crucial for RA pathogenesis. Moreover, increasing evidence has suggested that GRP78 participates in antibody generation, T cell proliferation, and pro-inflammatory cytokine production, and is therefore one of the potential therapeutic targets for RA. In this review, we discuss the putative, pathophysiological roles of ER stress and GRP78 in RA pathogenesis. The Korean Academy of Medical Sciences 2014-01 2013-12-26 /pmc/articles/PMC3890471/ /pubmed/24431899 http://dx.doi.org/10.3346/jkms.2014.29.1.2 Text en © 2014 The Korean Academy of Medical Sciences. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Park, Yune-Jung
Yoo, Seung-Ah
Kim, Wan-Uk
Role of Endoplasmic Reticulum Stress in Rheumatoid Arthritis Pathogenesis
title Role of Endoplasmic Reticulum Stress in Rheumatoid Arthritis Pathogenesis
title_full Role of Endoplasmic Reticulum Stress in Rheumatoid Arthritis Pathogenesis
title_fullStr Role of Endoplasmic Reticulum Stress in Rheumatoid Arthritis Pathogenesis
title_full_unstemmed Role of Endoplasmic Reticulum Stress in Rheumatoid Arthritis Pathogenesis
title_short Role of Endoplasmic Reticulum Stress in Rheumatoid Arthritis Pathogenesis
title_sort role of endoplasmic reticulum stress in rheumatoid arthritis pathogenesis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890471/
https://www.ncbi.nlm.nih.gov/pubmed/24431899
http://dx.doi.org/10.3346/jkms.2014.29.1.2
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