心筋梗塞後心臓リモデリングにおける筋線維芽細胞へのジメチルセレコキシブの作用の検討

• Published in: 日本薬理学会年会要旨集 p. 1-YIA-08
• Main Authors: 幾島, 栄悟, 高橋, 富美, 瀧口, 知浩, 豊平, 由美子, 石兼, 真
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2020
• Subjects: fibroblast; heart
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.93.0_1-YIA-08

【Background】Cardiac fibrosis is associated with heart diseases, such as myocardial infarction (MI), and activated fibroblasts (myofibroblasts) play a main role during fibrosis progression. Although we reported that 2,5 dimethylcelecoxib (DM-C) prevents cardiac fibrosis, the molecular mechanism, including the effect on myofibroblast differentiation, is not clarified yet.【Objective】We investigate the effect of DM-C on MI-caused fibrosis and fibroblast-myofibroblast differentiation using in vivo and in vitro models. 【Methods】In vivo: Cryoinjury-induced MI (CMI) mouse model was employed. In DM-C group, the mice received DM-C for 4 weeks from 3 days before the operation. Cardiac function was evaluated with transthoracic echocardiography every week. Four weeks after operation, the heart was removed and the fibrosis area was evaluated.In vitro: The effect DM-C on myofibroblast-differentiation induced by TGF-b using SD rat dermal fibroblast was examined.【Results】In DM-C group, the ejection fraction was increased than control group and, according with this, the fibrosis area is reduced. Further, DM-C significantly suppressed aSMA expression (myofibroblast marker) and the phosphorylation level of Akt, GSK-3b and Smad2/3.【Conclusion】These results suggest that DM-C attenuates cardiac fibrosis after MI through inhibition of fibroblast-myofibroblast differentiation. DM-C also inhibited the TGF-b /SMAD2/3 signaling pathway by Akt inhibition. Therefore, DM-C has a potential as the novel drug for treatment of cardiac fibrosis after MI.