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

Tanimura, Shun; Nishida, Mutsumi; Horie, Tatsunori; Kamishima, Tamotsu; Matsumoto, Hitomi; Morimura, Yutaka; Nishibata, Yuka; Masuda, Sakiko; Nakazawa, Daigo; Tomaru, Utano; Atsumi, Tatsuya; Ishizu, Akihiro

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

Tanimura, Shun; Nishida, Mutsumi; Horie, Tatsunori et al.

Experimental and Molecular Pathology, 2020, 115, 104454

Permalink : https://hdl.handle.net/2115/82338

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アクセス権	open access
URI	https://hdl.handle.net/2115/82338
タイトル	Fluvastatin prevents the development of arthritis in env-pX rats via up-regulation of Rho GTPase-activating protein 12
著者	Tanimura, Shun ; Nishida, Mutsumi ; Horie, Tatsunori ; Kamishima, Tamotsu ; Matsumoto, Hitomi ; Morimura, Yutaka ; Nishibata, Yuka ; Masuda, Sakiko ; Nakazawa, Daigo ; Tomaru, Utano ; Atsumi, Tatsuya ; Ishizu, Akihiro
著者名 Tanimura, Shun
e-Rad_Researcher 90404722 著者名 Nishida, Mutsumi
著者名 Horie, Tatsunori
e-Rad_Researcher 10399868 著者名 Kamishima, Tamotsu
著者名 Matsumoto, Hitomi
著者名 Morimura, Yutaka
著者名 Nishibata, Yuka
e-Rad_Researcher 10763617 著者名 Masuda, Sakiko
e-Rad_Researcher 60724135 著者名 Nakazawa, Daigo
e-Rad_Researcher 20360901 著者名 Tomaru, Utano
e-Rad_Researcher 20301905 著者名 Atsumi, Tatsuya
e-Rad_Researcher 60321957 著者名 Ishizu, Akihiro
言語	英語
キーワード	Rheumatoid arthritis
	Fluvastatin
	ARHGAP12
発行日	2020-08
出版者	Elsevier
収録物名	Experimental and Molecular Pathology
巻(号)	115
ページ	104454
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0014-4800
EISSN	1096-0945
関連情報	PMID 32422132
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.yexmp.2020.104454