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The Janus kinase inhibitor (baricitinib) suppresses the rheumatoid arthritis active marker gliostatin/thymidine phosphorylase in human fibroblast-like synoviocytes

Gliostatin/thymidine phosphorylase (GLS/TP) is known to have angiogenic and arthritogenic activities in the pathogenesis of rheumatoid arthritis (RA). The novel oral Janus kinase (JAK) inhibitor baricitinib has demonstrated high efficacy in RA. However, the effect of baricitinib on fibroblast-like s...

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Autores principales: Joyo, Yuji, Kawaguchi, Yohei, Yonezu, Hiroki, Senda, Hiroya, Yasuma, Sanshiro, Shiraga, Hiroo, Nozaki, Masahiro, Aoyama, Mineyoshi, Asai, Kiyofumi, Murakami, Hideki, Waguri-Nagaya, Yuko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917024/
https://www.ncbi.nlm.nih.gov/pubmed/35014010
http://dx.doi.org/10.1007/s12026-022-09261-4
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author Joyo, Yuji
Kawaguchi, Yohei
Yonezu, Hiroki
Senda, Hiroya
Yasuma, Sanshiro
Shiraga, Hiroo
Nozaki, Masahiro
Aoyama, Mineyoshi
Asai, Kiyofumi
Murakami, Hideki
Waguri-Nagaya, Yuko
author_facet Joyo, Yuji
Kawaguchi, Yohei
Yonezu, Hiroki
Senda, Hiroya
Yasuma, Sanshiro
Shiraga, Hiroo
Nozaki, Masahiro
Aoyama, Mineyoshi
Asai, Kiyofumi
Murakami, Hideki
Waguri-Nagaya, Yuko
author_sort Joyo, Yuji
collection PubMed
description Gliostatin/thymidine phosphorylase (GLS/TP) is known to have angiogenic and arthritogenic activities in the pathogenesis of rheumatoid arthritis (RA). The novel oral Janus kinase (JAK) inhibitor baricitinib has demonstrated high efficacy in RA. However, the effect of baricitinib on fibroblast-like synoviocytes (FLSs), a key component of invasive synovitis, has not been still elucidated. This study investigated whether GLS/TP production could be regulated by JAK/signal transducers and activators of transcription (STAT) signaling in FLSs derived from patients with RA. FLSs were cultured and stimulated by interferon (IFN)γ in the presence of baricitinib. Expression levels of GLS/TP were determined using reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunocytochemistry. Phosphorylation of STAT proteins was investigated by Western blot. In cultured FLSs, GLS/TP mRNA and protein levels were significantly induced by treatment with IFNγ and these inductions were suppressed by baricitinib treatment. Baricitinib inhibited IFNγ-induced STAT1 phosphorylation, while JAK/STAT activation played a pivotal role in IFNγ-mediated GLS/TP upregulation in RA. These results suggested that baricitinib suppressed IFNγ-induced GLS/TP expression by inhibiting JAK/STAT signaling, resulting in the attenuation of neovascularization, synovial inflammation, and cartilage destruction.
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spelling pubmed-89170242022-03-17 The Janus kinase inhibitor (baricitinib) suppresses the rheumatoid arthritis active marker gliostatin/thymidine phosphorylase in human fibroblast-like synoviocytes Joyo, Yuji Kawaguchi, Yohei Yonezu, Hiroki Senda, Hiroya Yasuma, Sanshiro Shiraga, Hiroo Nozaki, Masahiro Aoyama, Mineyoshi Asai, Kiyofumi Murakami, Hideki Waguri-Nagaya, Yuko Immunol Res Original Article Gliostatin/thymidine phosphorylase (GLS/TP) is known to have angiogenic and arthritogenic activities in the pathogenesis of rheumatoid arthritis (RA). The novel oral Janus kinase (JAK) inhibitor baricitinib has demonstrated high efficacy in RA. However, the effect of baricitinib on fibroblast-like synoviocytes (FLSs), a key component of invasive synovitis, has not been still elucidated. This study investigated whether GLS/TP production could be regulated by JAK/signal transducers and activators of transcription (STAT) signaling in FLSs derived from patients with RA. FLSs were cultured and stimulated by interferon (IFN)γ in the presence of baricitinib. Expression levels of GLS/TP were determined using reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunocytochemistry. Phosphorylation of STAT proteins was investigated by Western blot. In cultured FLSs, GLS/TP mRNA and protein levels were significantly induced by treatment with IFNγ and these inductions were suppressed by baricitinib treatment. Baricitinib inhibited IFNγ-induced STAT1 phosphorylation, while JAK/STAT activation played a pivotal role in IFNγ-mediated GLS/TP upregulation in RA. These results suggested that baricitinib suppressed IFNγ-induced GLS/TP expression by inhibiting JAK/STAT signaling, resulting in the attenuation of neovascularization, synovial inflammation, and cartilage destruction. Springer US 2022-01-10 2022 /pmc/articles/PMC8917024/ /pubmed/35014010 http://dx.doi.org/10.1007/s12026-022-09261-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Joyo, Yuji
Kawaguchi, Yohei
Yonezu, Hiroki
Senda, Hiroya
Yasuma, Sanshiro
Shiraga, Hiroo
Nozaki, Masahiro
Aoyama, Mineyoshi
Asai, Kiyofumi
Murakami, Hideki
Waguri-Nagaya, Yuko
The Janus kinase inhibitor (baricitinib) suppresses the rheumatoid arthritis active marker gliostatin/thymidine phosphorylase in human fibroblast-like synoviocytes
title The Janus kinase inhibitor (baricitinib) suppresses the rheumatoid arthritis active marker gliostatin/thymidine phosphorylase in human fibroblast-like synoviocytes
title_full The Janus kinase inhibitor (baricitinib) suppresses the rheumatoid arthritis active marker gliostatin/thymidine phosphorylase in human fibroblast-like synoviocytes
title_fullStr The Janus kinase inhibitor (baricitinib) suppresses the rheumatoid arthritis active marker gliostatin/thymidine phosphorylase in human fibroblast-like synoviocytes
title_full_unstemmed The Janus kinase inhibitor (baricitinib) suppresses the rheumatoid arthritis active marker gliostatin/thymidine phosphorylase in human fibroblast-like synoviocytes
title_short The Janus kinase inhibitor (baricitinib) suppresses the rheumatoid arthritis active marker gliostatin/thymidine phosphorylase in human fibroblast-like synoviocytes
title_sort janus kinase inhibitor (baricitinib) suppresses the rheumatoid arthritis active marker gliostatin/thymidine phosphorylase in human fibroblast-like synoviocytes
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917024/
https://www.ncbi.nlm.nih.gov/pubmed/35014010
http://dx.doi.org/10.1007/s12026-022-09261-4
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