[The activation of MAPK/cyclin D1-CDK4 signaling pathway caused by quartz]

Fu-Hai Shen1, Xue-Yun Fan, Bing-Ci Liu

  • 1National Institute of Occupational Health and Poisons Control, Chinese Center for Disease Control and Prevention, Beijing, China.

Abstract

Insights

Quartz exposure increases mitogen-activated protein kinase (MAPK) phosphorylation and cyclin D1-CDK4 expression in human embryonic lung fibroblasts. This suggests MAPK/AP-1 signaling mediates these changes in transformed cells.

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Context:

  • Quartz exposure is linked to cellular changes in human embryonic lung fibroblasts (HELF).
  • Understanding the molecular mechanisms behind quartz-induced cellular transformation is crucial for occupational health and safety.
  • The role of mitogen-activated protein kinase (MAPK) signaling in cellular responses to crystalline quartz requires further elucidation.

Purpose:

  • To investigate the phosphorylation status of MAPK pathways (ERK, p38, JNK) in HELF following quartz exposure.
  • To determine the expression levels of cyclin D1-CDK4 protein in quartz-transformed HELF (S-HELF).
  • To elucidate whether the MAPK/AP-1 signaling pathway mediates cyclin D1-CDK4 protein expression in S-HELF.

Summary:

  • Quartz exposure increased phosphorylation of ERK, p38, and JNK in HELF.
  • In S-HELF, ERK and JNK (p46) phosphorylation increased, while p38 phosphorylation decreased.
  • Cyclin D1 and CDK4 protein expression were elevated in S-HELF, and this was linked to ERK and JNK/AP-1 activation, but not p38.

Impact:

  • This study reveals that crystalline quartz can alter MAPK signaling and upregulate cell cycle proteins in lung fibroblasts.
  • The findings highlight the involvement of the ERK and JNK/AP-1 pathways in quartz-induced cellular transformation.
  • These insights contribute to understanding the pathogenesis of silicosis and other quartz-related lung diseases.

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