Use and application of nanoparticles has increased in recent years. Copper oxide nanoparticles (CuONPs) are one of the most common types of nanoparticles, and they are mainly used as catalysts and preservatives. However, limited toxicity data are available on the toxicity of CuONPs to the respiratory system. We investigated fibrotic responses induced by CuONPs in the respiratory tract and elucidated its underlying mechanism of action in vivo and in vitro experiments. In the mouse model, CuONPs exposure markedly increased transforming growth factor-β1 (TGF-β1) and collagen I expression and Smad3 phosphorylation, combined with elevation of inflammatory mediators including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). These alterations were also observed in histological analysis of lung tissue. CuONPs markedly increased inflammatory responses and collagen deposition, accompanied by the elevation of TGF-β1 and collagen I expression in lung tissue. In addition, CuONPs-treated H292 cells showed significantly increased mRNA and protein production of TGF-β1, collagen I, IL-6, and TNF-α; this response was markedly decreased by treatment of a TGF-β1 inhibitor (SB-431542). Taken together, CuONPs induced fibrotic responses in the respiratory tract, closely related to TGF-β1/Smad3 signaling. Therefore, our results raise the necessity of further investigation for the present state of its risk by providing useful information of the toxicity of CuONPs.

中文翻译：

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氧化铜纳米颗粒通过TGF-β1/ Smad3信号在人呼吸道上皮细胞中诱导胶原蛋白沉积

近年来，纳米粒子的使用和应用已经增加。氧化铜纳米颗粒（CuONPs）是最常见的纳米颗粒类型之一，它们主要用作催化剂和防腐剂。但是，关于CuONP对呼吸系统毒性的毒性数据有限。我们调查了CuONPs在呼吸道中诱导的纤维化反应，并阐明了其在体内和体外的潜在作用机制。实验。在小鼠模型中，CuONPs暴露显着增加了转化生长因子-β1（TGF-β1）和胶原蛋白I的表达以及Smad3磷酸化，并增加了包括白介素（IL）-1β，IL-6和肿瘤坏死因子-在内的炎症介质。 α（TNF-α）。在肺组织的组织学分析中也观察到了这些改变。CuONPs明显增加了炎症反应和胶原蛋白的沉积，并伴随着肺组织中TGF-β1和胶原蛋白I表达的升高。另外，用CuONPs处理的H292细胞显示出TGF-β1，胶原I，IL-6和TNF-α的mRNA和蛋白产生显着增加；通过治疗TGF-β1抑制剂（SB-431542），该反应显着降低。总之，CuONPs在呼吸道中诱导了纤维化反应，与TGF-β1/ Smad3信号传导密切相关。