Nickel nanoparticles induce epithelial-mesenchymal transition in human bronchial epithelial cells via the HIF-1α/HDAC3 pathway.
Nickel nanoparticles induce epithelial-mesenchymal transition in human bronchial epithelial cells via the HIF-1α/HDAC3 pathway.
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DOI：
10.1080/17435390.2022.2142169
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发表时间：
2022-08
期刊：
影响因子：
5
通讯作者：
Zhang, Qunwei
中科院分区：
文献类型：
--
作者：
Yuan, Jiali;Mo, Yiqun;Zhang, Yuanbao;Zhang, Yue;Zhang, Qunwei
关键词：
我们和其他人之前已经证明，暴露于镍纳米颗粒（纳米镍）会导致纤维形成和致癌作用；然而，其潜在机制仍未完全了解。本研究旨在探讨纳米ni对人支气管上皮细胞（BEAS-2B）上皮-间充质转化（EMT）的影响及其潜在机制，因为EMT既参与癌症发病也参与组织纤维化。我们的研究结果表明，与对照纳米tio2相比，纳米ni暴露可导致E-cadherin的表达显著降低，而vimentin和α-SMA的表达显著增加，表明纳米ni在人支气管上皮细胞EMT发育中起诱导作用。在纳米ni暴露的细胞中也观察到HIF-1α核聚集、HDAC3上调和组蛋白乙酰化降低，而在纳米tio2暴露的细胞中则没有。用特异性HIF-1α抑制剂CAY10585或HIF-1α特异性siRNAprior对纳米ni暴露的细胞进行预处理，可恢复E-cadherin，并消除纳米ni诱导的vimentin和α-SMA上调，这表明HIF-1α在纳米ni诱导的EMT发展中起着至关重要的作用。CAY10585预处理也能减弱HDAC3上调，增加组蛋白乙酰化。用特异性siRNA抑制HDAC3可显著抑制纳米镍诱导的组蛋白乙酰化降低，并将emt相关蛋白的表达储存到接近控制水平。综上所述，我们的研究结果表明，纳米ni暴露通过hif -1α-介导的HDAC3上调来降低组蛋白乙酰化，从而促进人支气管上皮细胞EMT的发展。我们的发现可能为进一步了解纳米镍诱导的纤维化和癌变的分子机制提供信息。
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 siRNAprior 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 restrainedNano-Ni-induced reduction in histone acetylation andrestored 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 provideinformation for further understanding of the molecular mechanisms of Nano-Ni-induced fibrosis and carcinogenesis.
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影响因子：
19
作者：
Bakir B;Chiarella AM;Pitarresi JR;Rustgi AK
通讯作者：
Rustgi AK
影响因子：
10.4
作者：
Gulino GR;Polimeni M;Prato M;Gazzano E;Kopecka J;Colombatto S;Ghigo D;Aldieri E
通讯作者：
Aldieri E
巨噬细胞中组蛋白乙酰化对白介素 6 的表观遗传调控及其在百草枯诱导的肺纤维化中的作用。
影响因子：
7.3
作者：
Hu L;Yu Y;Huang H;Fan H;Hu L;Yin C;Li K;Fulton DJ;Chen F
通讯作者：
Chen F
DOI：
10.1111/j.1600-6143.2012.04081.x
发表时间：
2012-08
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Djamali A;Reese S;Hafez O;Vidyasagar A;Jacobson L;Swain W;Kolehmainen C;Huang L;Wilson NA;Torrealba JR
通讯作者：
Torrealba JR
影响因子：
13.5
作者：
Kaimori, Aki;Potter, James J.;Koteish, Ayman A.
通讯作者：
Koteish, Ayman A.