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SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Cyclin-dependent Kinase 6 Gene

This study was performed to elucidate the molecular function of the synoviocyte proliferation-associated in collagen-induced arthritis (CIA) 1/serum amyloid A-like 1 (SPACIA1/SAAL1) in mice CIA, an animal model of rheumatoid arthritis (RA), and human RA-synovial fibroblasts (RASFs). SPACIA1/SAAL1-de...

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Autores principales: Fujii, Ryoji, Komatsu, Rie, Sato, Tomoo, Seki, Iwao, Konomi, Koji, Aono, Hiroyuki, Niki, Hisateru, Yudoh, Kazuo, Nishioka, Kusuki, Nakajima, Toshihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320788/
https://www.ncbi.nlm.nih.gov/pubmed/30513680
http://dx.doi.org/10.3390/ijms19123828
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author Fujii, Ryoji
Komatsu, Rie
Sato, Tomoo
Seki, Iwao
Konomi, Koji
Aono, Hiroyuki
Niki, Hisateru
Yudoh, Kazuo
Nishioka, Kusuki
Nakajima, Toshihiro
author_facet Fujii, Ryoji
Komatsu, Rie
Sato, Tomoo
Seki, Iwao
Konomi, Koji
Aono, Hiroyuki
Niki, Hisateru
Yudoh, Kazuo
Nishioka, Kusuki
Nakajima, Toshihiro
author_sort Fujii, Ryoji
collection PubMed
description This study was performed to elucidate the molecular function of the synoviocyte proliferation-associated in collagen-induced arthritis (CIA) 1/serum amyloid A-like 1 (SPACIA1/SAAL1) in mice CIA, an animal model of rheumatoid arthritis (RA), and human RA-synovial fibroblasts (RASFs). SPACIA1/SAAL1-deficient mice were generated and used to create mouse models of CIA in mild or severe disease conditions. Cell cycle-related genes, whose expression levels were affected by SPACIA1/SAAL1 small interfering RNA (siRNA), were screened. Transcriptional and post-transcriptional effects of SPACIA1/SAAL1 siRNA on cyclin-dependent kinase (cdk) 6 gene expression were investigated in human RASFs. SPACIA1/SAAL1-deficient mice showed later onset and slower progression of CIA than wild-type mice in severe disease conditions, but not in mild conditions. Expression levels of cdk6, but not cdk4, which are D-type cyclin partners, were downregulated by SPACIA1/SAAL1 siRNA at the post-transcriptional level. The exacerbation of CIA depends on SPACIA1/SAAL1 expression, although CIA also progresses slowly in the absence of SPACIA1/SAAL1. The CDK6, expression of which is up-regulated by the SPACIA1/SAAL1 expression, might be a critical factor in the exacerbation of CIA.
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spelling pubmed-63207882019-01-07 SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Cyclin-dependent Kinase 6 Gene Fujii, Ryoji Komatsu, Rie Sato, Tomoo Seki, Iwao Konomi, Koji Aono, Hiroyuki Niki, Hisateru Yudoh, Kazuo Nishioka, Kusuki Nakajima, Toshihiro Int J Mol Sci Article This study was performed to elucidate the molecular function of the synoviocyte proliferation-associated in collagen-induced arthritis (CIA) 1/serum amyloid A-like 1 (SPACIA1/SAAL1) in mice CIA, an animal model of rheumatoid arthritis (RA), and human RA-synovial fibroblasts (RASFs). SPACIA1/SAAL1-deficient mice were generated and used to create mouse models of CIA in mild or severe disease conditions. Cell cycle-related genes, whose expression levels were affected by SPACIA1/SAAL1 small interfering RNA (siRNA), were screened. Transcriptional and post-transcriptional effects of SPACIA1/SAAL1 siRNA on cyclin-dependent kinase (cdk) 6 gene expression were investigated in human RASFs. SPACIA1/SAAL1-deficient mice showed later onset and slower progression of CIA than wild-type mice in severe disease conditions, but not in mild conditions. Expression levels of cdk6, but not cdk4, which are D-type cyclin partners, were downregulated by SPACIA1/SAAL1 siRNA at the post-transcriptional level. The exacerbation of CIA depends on SPACIA1/SAAL1 expression, although CIA also progresses slowly in the absence of SPACIA1/SAAL1. The CDK6, expression of which is up-regulated by the SPACIA1/SAAL1 expression, might be a critical factor in the exacerbation of CIA. MDPI 2018-11-30 /pmc/articles/PMC6320788/ /pubmed/30513680 http://dx.doi.org/10.3390/ijms19123828 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fujii, Ryoji
Komatsu, Rie
Sato, Tomoo
Seki, Iwao
Konomi, Koji
Aono, Hiroyuki
Niki, Hisateru
Yudoh, Kazuo
Nishioka, Kusuki
Nakajima, Toshihiro
SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Cyclin-dependent Kinase 6 Gene
title SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Cyclin-dependent Kinase 6 Gene
title_full SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Cyclin-dependent Kinase 6 Gene
title_fullStr SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Cyclin-dependent Kinase 6 Gene
title_full_unstemmed SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Cyclin-dependent Kinase 6 Gene
title_short SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Cyclin-dependent Kinase 6 Gene
title_sort spacia1/saal1 deletion results in a moderate delay in collagen-induced arthritis activity, along with mrna decay of cyclin-dependent kinase 6 gene
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320788/
https://www.ncbi.nlm.nih.gov/pubmed/30513680
http://dx.doi.org/10.3390/ijms19123828
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