我们和其他人以前已经证明了暴露于镍纳米粒子（Nano-Ni）会导致纤维化和致癌作用，然而，其潜在机制仍未完全理解。这项研究旨在研究Nano-Ni对人支气管上皮细胞（BEAS-2B）上皮间质转化（EMT）的影响及其潜在机制，因为EMT涉及癌症发病和组织纤维化。我们的研究结果表明，与对照Nano-TiO2相比，接触Nano-Ni导致E-cadherin表达显著下降，vimentin和α-SMA表达增加，说明Nano-Ni在人支气管上皮细胞的EMT发展中发挥着可诱发的作用。细胞暴露于Nano-Ni时，观察到HIF-1α核积累、HDAC3上调和组蛋白乙酰化降低，而暴露于Nano-TiO2的细胞未观察到这些现象。细胞在暴露于Nano-Ni之前使用特异性HIF-1α抑制剂CAY10585或HIF-1α特异性siRNA转染，导致E-cadherin的修复以及消除Nano-Ni诱导的vimentin和α-SMA上调，提示HIF-1α在Nano-Ni诱导的EMT发展中发挥着关键作用。CAY10585预处理还减轻了HDAC3上调和组蛋白乙酰化增加。使用特异性siRNA抑制HDAC3可显著抑制Nano-Ni诱导的组蛋白乙酰化降低，并将EMT相关蛋白表达恢复至接近对照水平。总之，我们的研究结果表明，暴露于Nano-Ni，通过HIF-1α介导的HDAC3上调降低组蛋白乙酰化促进了人支气管上皮细胞中EMT的发展。这些发现可为更进一步理解Nano-Ni导致的纤维化和致癌分子机制提供信息。

We and others have previously demonstrated that exposure to nickel nanoparticles (Nano-Ni) caused fibrogenic and carcinogenic effects; however, the underlying mechanisms are still not fully understood. This study aimed to investigate the effects of Nano-Ni on epithelial-mesenchymal transition (EMT) in human bronchial epithelial cells (BEAS-2B) and its underlying mechanisms since EMT is involved in both cancer pathogenesis and tissue fibrosis. Our results showed that exposure to Nano-Ni, compared to the control Nano-TiO2, caused a remarkable decrease in the expression of E-cadherin and an increase in the expression of vimentin and α-SMA, indicating an inducible role of Nano-Ni in EMT development in human bronchial epithelial cells. HIF-1α nuclear accumulation, HDAC3 upregulation, and decreased histone acetylation were also observed in the cells exposed to Nano-Ni, but not in those exposed to Nano-TiO2. Pretreatment of the cells with a specific HIF-1α inhibitor, CAY10585, or HIF-1α-specific siRNA transfection prior to Nano-Ni exposure resulted in the restoration of E-cadherin and abolished Nano-Ni-induced upregulation of vimentin and α-SMA, suggesting a crucial role of HIF-1α in Nano-Ni-induced EMT development. CAY10585 pretreatment also attenuated the HDAC3 upregulation and increased histone acetylation. Inhibition of HDAC3 with specific siRNA significantly restrained Nano-Ni-induced reduction in histone acetylation and restored EMT-related protein expression to near control levels. In summary, our findings suggest that exposure to Nano-Ni promotes the development of EMT in human bronchial epithelial cells by decreasing histone acetylation through HIF-1α-mediated HDAC3 upregulation. Our findings may provide information for further understanding of the molecular mechanisms of Nano-Ni-induced fibrosis and carcinogenesis.