Department of Occupational and Environmental Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian, 116044, China.
Dalian Municipal Center for Disease Control & Prevention, Dalian, 116023, China.
Chem Biol Interact. 2017 Nov 1;277:1-7. doi: 10.1016/j.cbi.2017.08.012. Epub 2017 Aug 19.
Cadmium (Cd) is a toxic metal widely found in a number of environmental matrices, and it induces serious adverse effects in various organs and tissues. In this study, the role of high mobility group A2 (HMGA2) in promoting migration and invasion in Cd-treated A549 cells and lung tissues of mice was investigated. Our findings showed that exposure to Cd (2 μM) for 48 h or subcutaneous injection of Cd daily for 6 weeks significantly enhanced the expression of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), phosphorylated focal adhesion kinase (p-FAK), and HMGA2 in A549 cells or lung tissues of mice. In A549 cells, HMGA2 knockdown significantly decreased expression of MMP-9, MMP-2 and p-FAK and inhibited the migration and invasion compared to that of only Cd-treated cultures. Overexpression of HMGA2 in HEK-293T cells increased expression of MMP-9, MMP-2 and p-FAK and enhanced the migration and invasion compared with the empty vector transfection group. In conclusion, upregulation of HMGA2 plays an important role in Cd-enhanced migration and invasion. Suppressing HMGA2 expression might have potential values in prevention of Cd-resulted toxicities.
镉 (Cd) 是一种广泛存在于多种环境基质中的有毒金属,它会对各种器官和组织造成严重的不良影响。在这项研究中,研究了高迁移率族蛋白 A2 (HMGA2) 在促进 Cd 处理的 A549 细胞迁移和侵袭以及小鼠肺组织中的作用。研究结果表明,暴露于 2 μM Cd 48 h 或每天皮下注射 Cd 6 周,可显著增强 A549 细胞或小鼠肺组织中基质金属蛋白酶 9 (MMP-9)、基质金属蛋白酶 2 (MMP-2)、磷酸化粘着斑激酶 (p-FAK) 和 HMGA2 的表达。在 A549 细胞中,与仅用 Cd 处理的细胞相比,HMGA2 敲低可显著降低 MMP-9、MMP-2 和 p-FAK 的表达,并抑制迁移和侵袭。与空载体转染组相比,HEK-293T 细胞中 HMGA2 的过表达可增加 MMP-9、MMP-2 和 p-FAK 的表达,并增强迁移和侵袭。总之,HMGA2 的上调在 Cd 增强的迁移和侵袭中起重要作用。抑制 HMGA2 的表达可能对预防 Cd 毒性具有潜在价值。