雷洛昔芬
三苯氧胺
磷酸化
选择性雌激素受体调节剂
MAPK/ERK通路
NADPH氧化酶
信号转导
癌症研究
细胞生物学
药理学
活性氧
化学
生物
内科学
医学
癌症
乳腺癌
作者
Vahid Zarezade,Narges Mohammadtaghvaei,Mojtaba Rashidi,Hossein Babaahmadi-Rezaei
标识
DOI:10.1016/j.bbrc.2023.06.031
摘要
Atherosclerosis, a leading cause of cardiovascular disease, remains a significant global health concern. Tamoxifen and raloxifene, selective estrogen receptor modulators (SERMs), have demonstrated potential cardioprotective effects. However, the underlying molecular mechanisms by which these SERMs modulate Transforming Growth Factor-β (TGF-β) signaling in human vascular smooth muscle cells (VSMCs) remain largely unexplored. This study sought to investigate the impact of tamoxifen and raloxifene on TGF-β-induced CHSY1 expression and Smad2 linker region phosphorylation in VSMCs and to elucidate the role of reactive oxygen species (ROS), NADPH oxidase (NOX), and kinase pathways in mediating these effects. Employing a comprehensive experimental strategy, VSMCs were treated with TGF-β in the presence or absence of tamoxifen, raloxifene, and various pharmacological inhibitors. Subsequently, CHSY1 mRNA expression, Smad2C and Smad2L phosphorylation, ROS production, p47phox and ERK 1/2 phosphorylation were assessed. Our results revealed that tamoxifen and raloxifene significantly attenuated TGF-β-mediated CHSY1 mRNA expression and Smad2 linker region phosphorylation, without affecting the canonical TGF-β-Smad2C pathway. Furthermore, these compounds effectively inhibited ROS production, p47phox and ERK 1/2 phosphorylation, implicating the involvement of the TGF-β-NOX-ERK-Smad2L signaling cascade in their cardioprotective properties. This study provides a comprehensive understanding of the molecular mechanisms underlying the cardioprotective effects of tamoxifen and raloxifene in VSMCs, offering valuable insights for the development of targeted therapeutic strategies aimed at atherosclerosis prevention and the promotion of cardiovascular health.
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