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

被引：0

作者：

Tanimura, Shun ^{[1
,2
]}

Nishida, Mutsumi ^{[3
]}

Horie, Tatsunori ^{[4
]}

Kamishima, Tamotsu ^{[5
]}

Matsumoto, Hitomi ^{[6
]}

Morimura, Yutaka ^{[6
]}

Nishibata, Yuka ^{[6
]}

Masuda, Sakiko ^{[6
]}

Nakazawa, Daigo ^{[1
,2
]}

Tomaru, Utano ^{[2
,7
]}

Atsumi, Tatsuya ^{[1
,2
]}

Ishizu, Akihiro ^{[6
]}

机构：

[1] Hokkaido Univ, Fac Med, Dept Rheumatol Endocrinol & Nephrol, Sapporo, Hokkaido, Japan

[2] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan

[3] Hokkaido Univ Hosp, Div Lab & Transfus Med, Sapporo, Hokkaido, Japan

[4] Hokkaido Univ Hosp, Dept Radiol Technol, Sapporo, Hokkaido, Japan

[5] Hokkaido Univ, Fac Hlth Sci, Dept Biomed Sci & Engn, Sapporo, Hokkaido, Japan

[6] Hokkaido Univ, Fac Hlth Sci, Dept Med Lab Sci, Sapporo, Hokkaido, Japan

[7] Hokkaido Univ, Fac Med, Dept Pathol, Sapporo, Hokkaido, Japan

来源：

EXPERIMENTAL AND MOLECULAR PATHOLOGY | 2020年 / 115卷

关键词：

Rheumatoid arthritis; Fluvastatin; ARHGAP12; FIBROBLAST-LIKE SYNOVIOCYTES; INDUCED RHEUMATOID-ARTHRITIS; NF-KAPPA-B; SIMVASTATIN; CELLS; GENE; ATORVASTATIN; COMBINATION; ULTRASOUND; EXPRESSION;

D O I：

10.1016/j.yexmp.2020.104454

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

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 mu g/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 nonarthritic 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.

引用

页数：7