{"title":"The protective role of glucocerebrosidase/ceramide in rheumatoid arthritis.","authors":"Mingfeng Yang, Juanfang Gu, Fangyan Xu, Yiwen Wang, Hongzhi Wang, Bin Zhang","doi":"10.1080/03008207.2022.2055552","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To clarify the role of glucocerebrosidase (GBA) and Ceramide (Cer) in rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>GBA-expressing lentivirus were constructed and injected into collagen-induced arthritis (CIA) mice, and compared with CIA mice injected with empty vector. The severity of arthritis and inflammatory mediators were evaluated. Fibroblast-like synoviocytes (FLS) from RA patients were transfected with GBA-expressing lentivirus, or pretreated with C6-Cer. The migration and invasion of FLS, the production of inflammatory cytokines, and the relevant signaling pathways were assessed.</p><p><strong>Results: </strong>In CIA mice, GBA markedly improved arthritis compared to that in the CIA mice, with increased content of proteoglycan and integral cartilage surfaces and tidemarks. The circulating inflammatory mediators, including interleukin (IL)-1β, IL-6, IL-18, and matrix metalloproteinase (MMP)-1, were significantly reduced in CIA mice with GBA overexpression compared to those in CIA mice. GBA and C6-Cer treatment inhibited migration and invasion of FLS, and suppressed production of inflammatory cytokines and activation of the MAPK pathways.</p><p><strong>Conclusion: </strong>GBA/Cer exhibited a protective role in CIA mice and RA FLS. These results highlight the potential of targeting GBA/Cer as a therapeutic strategy in RA and warrant further investigation.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Connective Tissue Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/03008207.2022.2055552","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/3/21 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 2
Abstract
Objective: To clarify the role of glucocerebrosidase (GBA) and Ceramide (Cer) in rheumatoid arthritis (RA).
Methods: GBA-expressing lentivirus were constructed and injected into collagen-induced arthritis (CIA) mice, and compared with CIA mice injected with empty vector. The severity of arthritis and inflammatory mediators were evaluated. Fibroblast-like synoviocytes (FLS) from RA patients were transfected with GBA-expressing lentivirus, or pretreated with C6-Cer. The migration and invasion of FLS, the production of inflammatory cytokines, and the relevant signaling pathways were assessed.
Results: In CIA mice, GBA markedly improved arthritis compared to that in the CIA mice, with increased content of proteoglycan and integral cartilage surfaces and tidemarks. The circulating inflammatory mediators, including interleukin (IL)-1β, IL-6, IL-18, and matrix metalloproteinase (MMP)-1, were significantly reduced in CIA mice with GBA overexpression compared to those in CIA mice. GBA and C6-Cer treatment inhibited migration and invasion of FLS, and suppressed production of inflammatory cytokines and activation of the MAPK pathways.
Conclusion: GBA/Cer exhibited a protective role in CIA mice and RA FLS. These results highlight the potential of targeting GBA/Cer as a therapeutic strategy in RA and warrant further investigation.
期刊介绍:
The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology.
The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented.
The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including
Biochemistry
Cell and Molecular Biology
Immunology
Structural Biology
Biophysics
Biomechanics
Regenerative Medicine
The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.