细胞周期蛋白D1
细胞周期
MAPK/ERK通路
细胞生物学
激酶
细胞周期蛋白依赖激酶4
细胞周期蛋白D
细胞周期蛋白
生物
细胞周期蛋白
化学
分子生物学
细胞
MAP激酶激酶激酶
生物化学
作者
Xiaowei Jia,Bingci Liu,Xianglin Shi,Meng Ye,Fengmei Zhang,Haifeng Liu
摘要
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 NH 2 ‐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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