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

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.

Journal

• Experimental and Molecular Pathology

  Experimental and Molecular Pathology 115 104454-, 2020-08

  Elsevier

Keywords

• Rheumatoid arthritis
• Fluvastatin
• ARHGAP12

Details

• CRID: 1050007515086332416
• NII Article ID: 120007126051
• DOI: 10.1016/j.yexmp.2020.104454
• ISSN: 10960945
• ISSN: 00144800
• HANDLE: 2115/82338
• Web Site: https://api.elsevier.com/content/article/PII:S0014480020300629?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0014480020300629?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN