title: ROS-dependent HMGA2 upregulation mediates Cd-induced proliferation in MRC-5 cells.
abstract: Cadmium (Cd) is a heavy metal widely found in a number of environmental matrices, and the exposure to Cd is increasing nowadays. In this study, the role of high mobility group A2 (HMGA2) in Cd-induced proliferation was investigated in MRC-5 cells. Exposure to Cd (2μM) for 48h significantly enhanced the growth of MRC-5 cells, increased reactive oxygen species (ROS) production, and induced both mRNA and protein expression of HMGA2. Evidence for Cd-induced reduction of the number of G0/G1 phase cells and an increase in the number of cells in S phase and G2/M phase was sought by flow cytometric analysis. Western blot analysis showed that cyclin D1, cyclin B1, and cyclin E were upregulated in Cd-treated cells. Further study revealed that N-acetyl cysteine (NAC) markedly prevented Cd-induced proliferation of MRC-5 cells, ROS generation, and the increasing protein level of HMGA2. Silencing of HMGA2 gene by siRNA blocked Cd-induced cyclin D1, cyclin B1, and cyclin E expression and reduction of the number of G0/G1 phase cells. Combining, our data showed that Cd-induced ROS formation provoked HMGA2 upregulation, caused cell cycle changes, and led to cell proliferation. This suggests that HMGA2 might be an important biomarker in Cd-induced cell proliferation.
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian 116044, China.
authors.forename: Huaying
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian 116044, China; Jilin Province Research Institute for Tuberculosis Prevention and Treatment, No. 3145. Jing yang Road, Changchun 130062, China.
authors.forename: Jiayue
authors.initials: J
authors.lastname: Wang
authors.affiliation: Liaoning Anti-Degenerative Diseases Natural Products Engineering Technology Research Center, Dalian Medical University, Dalian 116044, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Liaoning Anti-Degenerative Diseases Natural Products Engineering Technology Research Center, Dalian Medical University, Dalian 116044, China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Geng
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian 116044, China.
authors.forename: Qiujuan
authors.initials: Q
authors.lastname: Li
authors.affiliation: Dalian Municipal Center for Disease Control and Prevention, Dalian 116023, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Mei
authors.affiliation: Dalian Municipal Center for Disease Control and Prevention, Dalian 116023, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian 116044, China. Electronic address: caojunly@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
mesh_terms: D019256:Cadmium Chloride / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D025743:HMGA2 Protein / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D025743:HMGA2 Protein; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019256:Cadmium Chloride
keywords: Cadmium; Cell cycle; Cell proliferation; HMGA2; MRC-5 cells; ROS