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Fluvastatin prevents the development of arthritis in env-pX rats via up-regulation of Rho GTPase-activating protein 12

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Title: Fluvastatin prevents the development of arthritis in env-pX rats via up-regulation of Rho GTPase-activating protein 12
Authors: Tanimura, Shun Browse this author
Nishida, Mutsumi Browse this author →KAKEN DB
Horie, Tatsunori Browse this author
Kamishima, Tamotsu Browse this author →KAKEN DB
Matsumoto, Hitomi Browse this author
Morimura, Yutaka Browse this author
Nishibata, Yuka Browse this author
Masuda, Sakiko Browse this author →KAKEN DB
Nakazawa, Daigo Browse this author →KAKEN DB
Tomaru, Utano Browse this author →KAKEN DB
Atsumi, Tatsuya Browse this author →KAKEN DB
Ishizu, Akihiro Browse this author →KAKEN DB
Keywords: Rheumatoid arthritis
Issue Date: Aug-2020
Publisher: Elsevier
Journal Title: Experimental and Molecular Pathology
Volume: 115
Start Page: 104454
Publisher DOI: 10.1016/j.yexmp.2020.104454
PMID: 32422132
Abstract: The pleiotropic effects of statins, including an antiarthritic potential, have been noted. This study aimed to determine the efficacy of statins on rheumatoid arthritis (RA) and clarify how statins affect its pathogenesis. Fluvastatin (500 μg/kg/day) or vehicle was given per os to env-pX rats, which carry the human T-cell leukemia virus type I env-pX gene and spontaneously develop destructive arthritis mimicking RA, for 30 days. Blood sampling and ultrasonography (US) of the ankle joints were conducted on days 0, 10, 20, and 30. On day 30, all rats were euthanized, and the ankle joints were subjected to histological analysis. To clarify how fluvastatin affects the pathogenesis of RA, comprehensive serum exosomal microRNA (miRNA) analysis was performed. Gene expression in the primary culture of synovial fibroblasts derived from arthritic rat and human and non-arthritic rat periarticular tissues was determined quantitatively by real-time reverse transcription-polymerase chain reaction (RT-PCR). As a result, the development of arthritis in env-pX rats was significantly suppressed by fluvastatin, which was evident from the viewpoints of serology, US imaging, and histology. Comprehensive serum exosomal miRNA analysis suggested that the expression of Rho GTPase-activating protein 12 (Arhgap12) was decreased in arthritic env-pX rats but increased with the administration of fluvastatin. Corresponding results were obtained by quantitative RT- PCR using primary culture of synovial fibroblasts. The collective findings suggest that fluvastatin prevents the development of arthritis in env-pX rats via the up-regulation of ARHGAP12. This study suggests that ARHGAP12 can be a possible therapeutic target of RA.
Rights: © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 石津 明洋

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