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暴露于亚洲沙尘-颗粒物对人肝癌细胞和小鼠肝组织中 Tenascin-C 表达的影响。

Effect of exposure to Asian sand dust-Particulate matter on liver Tenascin-C expression in human cancer cell and mouse hepatic tissue.

机构信息

Department of Health Sciences and Technology, GAIHST, Gachon University, Korea.

Department of Life Science, College of BIONANO, Gachon University, Korea.

出版信息

J Toxicol Sci. 2019;44(9):633-641. doi: 10.2131/jts.44.633.

Abstract

Asian Sand Dust-Particulate Matter (ASD-PM) aerosol brings large amounts of wind-eroded soil particles containing high concentrations of metallic components caused by industrialization and vehicles. Proinflammatory and cytotoxic cytokines trigger local inflammatory responses and cause a systematically high incidence of cardiovascular and other diseases. Tenascin C (Tn-C) is known to be expressed in damaged tissue or in a developmental stage of tissue. In this study, we examined the expression of Tn-C and Fibronectin in human cancer-cell lines and in liver tissue of mice treated with ASD-PM to investigate the inflammatory and cell-damage effects of ASD-PM. In our in vivo study, mice were intratracheally instilled with saline suspensions of ASD-PM particles. Instillation of these particles was repeated twice a week for 12 weeks and the liver tissues were stained with hematoxylin, eosin, and Masson's trichrome, and we carried out an IF. Tn-C expression in liver tissues was detected by RT-PCR and western blot analysis. In the results, the expression of Tn-C increased in a dose-dependent manner in both RNA and Immunofluorescence assay (IF). In our in vitro study, A549 and Hep3B cell lines were incubated in culture media with Transforming Growth Factor-Beta1(TGF-β1) and ASD-PM. Immunofluorescence microscopy images showed a two times stronger expression of fluorescence in the ASD-treated group than in that treated with TGF-β1. They also showed a stronger expression of Tn-C in proportion to the concentration of ASD-PM. We confirmed that ASD-PM when inhaled formally migrated to other organs and induced Tn-C expression. ASD-PM containing metals causes expression of Tn-C in liver tissue in proportion to the concentration of ASD-PM.

摘要

亚洲沙尘颗粒物(ASD-PM)气溶胶携带大量风蚀土壤颗粒,其中含有工业化和车辆产生的高浓度金属成分。促炎和细胞毒性细胞因子引发局部炎症反应,导致心血管等疾病的系统高发。众所周知,Tenascin C(Tn-C)在受损组织或组织的发育阶段表达。在这项研究中,我们检查了 Tn-C 和纤连蛋白在人类癌细胞系和用 ASD-PM 处理的小鼠肝组织中的表达,以研究 ASD-PM 的炎症和细胞损伤作用。在我们的体内研究中,我们将 ASD-PM 颗粒的生理盐水混悬液经气管内滴注到小鼠体内。每周两次重复滴注这些颗粒 12 周,并对肝组织进行苏木精、伊红和 Masson 三色染色,同时进行免疫荧光染色。我们通过 RT-PCR 和 Western blot 分析检测肝组织中 Tn-C 的表达。结果显示,肝组织中 Tn-C 的表达在 RNA 和免疫荧光检测(IF)中均呈剂量依赖性增加。在我们的体外研究中,我们将 A549 和 Hep3B 细胞系在含有转化生长因子-β1(TGF-β1)和 ASD-PM 的培养基中孵育。免疫荧光显微镜图像显示,ASD 处理组的荧光表达强度是 TGF-β1 处理组的两倍。它们还显示 Tn-C 的表达与 ASD-PM 的浓度成正比。我们证实,吸入的 ASD-PM 正式迁移到其他器官,并诱导 Tn-C 的表达。含金属的 ASD-PM 会导致肝组织中 Tn-C 的表达与 ASD-PM 的浓度成正比。

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