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Semaphorin 3G exace...
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Shoda, JumpeiChiba Univ, Grad Sch Med, Dept Allergy & Clin Immunol, Chiba, Japan.;Chiba Univ, Grad Sch Med, Dept Orthoped Surg, Chiba, Japan.
(författare)
Semaphorin 3G exacerbates joint inflammation through the accumulation and proliferation of macrophages in the synovium
- Artikel/kapitelEngelska2022
Förlag, utgivningsår, omfång ...
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2022-06-04
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BioMed Central (BMC),2022
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-477759
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-477759URI
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https://doi.org/10.1186/s13075-022-02817-7DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Objectives Methotrexate (MTX) is an anchor drug for the treatment of rheumatoid arthritis (RA). However, the precise mechanisms by which MTX stalls RA progression and alleviates the ensuing disease effects remain unknown. The aim of the present study was to identify novel therapeutic target molecules, the expression patterns of which are affected by MTX in patients with RA. Methods CD4(+) T cells from 28 treatment-naive patients with RA before and 3 months after the initiation of MTX treatment were subjected to DNA microarray analyses. The expression levels of semaphorin 3G, a differentially expressed gene, and its receptor, neuropilin-2, were evaluated in the RA synovium and collagen-induced arthritis synovium. Collagen-induced arthritis and collagen antibody-induced arthritis were induced in semaphorin3G-deficient mice and control mice, and the clinical score, histological score, and serum cytokines were assessed. The migration and proliferation of semaphorin 3G-stimulated bone marrow-derived macrophages were analyzed in vitro. The effect of local semaphorin 3G administration on the clinical score and number of infiltrating macrophages during collagen antibody-induced arthritis was evaluated. Results Semaphorin 3G expression in CD4(+) T cells was downregulated by MTX treatment in RA patients. It was determined that semaphorin 3G is expressed in RA but not in the osteoarthritis synovium; its receptor neuropilin-2 is primarily expressed on activated macrophages. Semaphorin3G deficiency ameliorated collagen-induced arthritis and collagen antibody-induced arthritis. Semaphorin 3G stimulation enhanced the migration and proliferation of bone marrow-derived macrophages. Local administration of semaphorin 3G deteriorated collagen antibody-induced arthritis and increased the number of infiltrating macrophages. Conclusions Upregulation of semaphorin 3G in the RA synovium is a novel mechanism that exacerbates joint inflammation, leading to further deterioration, through macrophage accumulation.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Tanaka, ShigeruChiba Univ, Grad Sch Med, Dept Allergy & Clin Immunol, Chiba, Japan.
(författare)
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Etori, KeishiChiba Univ, Grad Sch Med, Dept Allergy & Clin Immunol, Chiba, Japan.
(författare)
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Hattori, KotoChiba Univ, Grad Sch Med, Dept Allergy & Clin Immunol, Chiba, Japan.
(författare)
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Kasuya, TadamichiChiba Univ, Grad Sch Med, Dept Allergy & Clin Immunol, Chiba, Japan.
(författare)
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Ikeda, KeiChiba Univ, Grad Sch Med, Dept Allergy & Clin Immunol, Chiba, Japan.
(författare)
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Maezawa, YukoChiba Univ, Grad Sch Med, Dept Allergy & Clin Immunol, Chiba, Japan.
(författare)
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Suto, AkiraChiba Univ, Grad Sch Med, Dept Allergy & Clin Immunol, Chiba, Japan.
(författare)
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Suzuki, KotaroChiba Univ, Grad Sch Med, Dept Allergy & Clin Immunol, Chiba, Japan.
(författare)
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Nakamura, JunichiChiba Univ, Grad Sch Med, Dept Orthoped Surg, Chiba, Japan.
(författare)
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Maezawa, YoshiroChiba Univ, Grad Sch Med, Dept Endocrinol Hematol & Gerontol, Chiba, Japan.
(författare)
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Takemoto, MinoruChiba Univ, Grad Sch Med, Dept Endocrinol Hematol & Gerontol, Chiba, Japan.;Int Univ Hlth & Welf, Dept Med, Div Diabet Metab & Endocrinol, Narita, Japan.
(författare)
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Betsholtz, ChristerUppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)chbet517
(författare)
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Yokote, KoutaroChiba Univ, Grad Sch Med, Dept Endocrinol Hematol & Gerontol, Chiba, Japan.
(författare)
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Ohtori, SeijiChiba Univ, Grad Sch Med, Dept Orthoped Surg, Chiba, Japan.
(författare)
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Nakajima, HiroshiChiba Univ, Grad Sch Med, Dept Allergy & Clin Immunol, Chiba, Japan.
(författare)
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Chiba Univ, Grad Sch Med, Dept Allergy & Clin Immunol, Chiba, Japan.;Chiba Univ, Grad Sch Med, Dept Orthoped Surg, Chiba, Japan.Chiba Univ, Grad Sch Med, Dept Allergy & Clin Immunol, Chiba, Japan.
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Arthritis Research & Therapy: BioMed Central (BMC)24:11478-63541478-6362
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Shoda, Jumpei
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Tanaka, Shigeru
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Etori, Keishi
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Hattori, Koto
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Kasuya, Tadamich ...
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Ikeda, Kei
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Maezawa, Yuko
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Suto, Akira
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Suzuki, Kotaro
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Nakamura, Junich ...
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Maezawa, Yoshiro
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Takemoto, Minoru
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Betsholtz, Chris ...
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Yokote, Koutaro
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Ohtori, Seiji
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Nakajima, Hirosh ...
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