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Roles of the ERK, JNK/AP-1/cyclin D1–CDK4 pathway in silica-induced cell cycle changes in human embryo lung fibroblast cells

Authors

  • Xiaowei Jia,

    1. National Institute of Occupation Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, Peoples Republic of China
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  • Bingci Liu,

    Corresponding author
    1. National Institute of Occupation Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, Peoples Republic of China
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  • Xianglin Shi,

    1. Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV 20505, U.S.A.
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  • Meng Ye,

    1. National Institute of Occupation Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, Peoples Republic of China
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  • Fengmei Zhang,

    1. Institute of Occupational and Environmental, School of Public Health, Shandong University, Jinan 250012, Shandong Province, Peoples Republic of China
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  • Haifeng Liu

    1. Tangshan Center for Disease Control and Prevention, Tangshan, Peoples Republic of China
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To whom correspondence should be addressed (email bcliu@263.net).

Abstract

Silica is a potent occupational fibrogenic agent capable of inducing lung fibrosis and many other lung diseases. Our current study focused on the signalling pathways regulating cell cycle changes in HELF (human embryo lung fibroblast) after silica (α-quartz) exposure. Our results showed silica exposure could lead to cell cycle changes. The cell cycle alternations were accompanied with overexpression of cyclin D1 and CDK4 (cyclin-dependent kinase 4) in a time-dependent manner. Silica exposure also decreased E2F-4 expression in HELF. These changes were blocked by overexpression of dominant-negative mutants of ERK (extracellular signal-regulated protein kinase) or the JNK (stress-activated c-Jun NH2-terminal kinase), respectively. Moreover, pretreatment of cells with curcumin, an activation of AP-1 (activator protein-1) inhibitor, inhibited silica-induced cell cycle alteration, the decreased expression of E2F-4 and overexpression of cyclin D1 and CDK4. Furthermore, both antisense cyclin D1 and antisense CDK4 can block silica-induced cell cycle changes. These results suggest that silica exposure can induce cell cycle changes, which may be mediated through ERK, JNK/AP-1/cyclin D1–CDK4-dependent pathway.

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