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標題: | Genistein suppresses leptin-induced proliferation and migration of vascular smooth muscle cells and neointima formation |
作者: | Tsai, Yung-Chieh Leu, Sy-Ying Peng, Yi-Jen Lee, Yen-Mei Hsu, Chih-Hsiung Chou, Shen-Chieh Yen, Mao-Hsiung Cheng, Pao-Yun |
貢獻者: | Chi Mei Med Ctr, Dept Obstet & Gynecol Taipei Med Univ, Dept Med Chia Nan Univ Pharm & Sci, Dept Sport Management Natl Def Med Ctr, Grad Inst Life Sci Triserv Gen Hosp, Dept Pathol Natl Def Med Ctr Natl Def Med Ctr, Dept Pharmacol Triserv Gen Hosp, Dept Internal Med, Natl Def Med Ctr China Med Univ, Dept Biol Sci & Technol, Coll Biopharmaceut & Food Sci Natl Def Med Ctr, Grad Inst Physiol, Dept Physiol & Biophys |
關鍵字: | genistein Leptin MMP2 carotid artery injury reactive oxygen species |
日期: | 2017-03 |
上傳時間: | 2018-11-30 15:53:03 (UTC+8) |
出版者: | Wiley |
摘要: | Obesity is a strong risk factor for the development of cardiovascular diseases and is associated with a marked increase in circulating leptin concentration. Leptin is a peptide hormone mainly produced by adipose tissue and is regulated by energy level, hormones and various inflammatory mediators. Genistein is an isoflavone that exhibits diverse health-promoting effects. Here, we investigated whether genistein suppressed the atherogenic effect induced by leptin. The A10 cells were treated with leptin and/or genistein, and then the cell proliferation and migration were analysed. The reactive oxygen species (ROS) and proteins levels were also measured, such as p44/42MAPK, cell cycle-related protein (cyclin D1 and p21) and matrix metalloproteinase-2 (MMP-2). Immunohistochemistry and morphometric analysis were used for the neointima formation in a rat carotid artery injury model. Genistein (5 mu M) significantly inhibited both the proliferation and migration of leptin (10 ng/ml)stimulated A10 cells. In accordance with these finding, genistein decreased the leptin-stimulated ROS production and phosphorylation of the p44/42MAPK signal transduction pathway. Meanwhile, genistein reversed the leptin-induced expression of cyclin D1, and cyclin-dependent kinase inhibitor, p21. Genistein attenuated leptin-induced A10 cell migration by inhibiting MMP-2 activity. Furthermore, the leptin (0.25 mg/kg)augmented neointima formation in a rat carotid artery injury model was attenuated in the genistein (5 mg/kg body weight)-treated group when compared with the balloon injury plus leptin group. Genistein was capable of suppressing the atherogenic effects of leptin in vitro and in vivo, and may be a promising candidate drug in the clinical setting. |
關聯: | Journal of Cellular and Molecular Medicine, v.21, n.3, pp.422-431 |
顯示於類別: | [運動管理系] 期刊論文
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