Gadolinium promoted proliferation in mouse embryo fibroblast NIH3T3 cells through Rac and PI3K/Akt signaling pathways

Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder disease developed in patients with underlying renal insufficiency following exposure to gadolinium-based contrast agents (GBCAs). Previous studies have demonstrated that GdCl 3 can promote NIH3T3 fibroblast cell proliferation, which provide...

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Bibliographic Details
Published in:Biometals 2014-08, Vol.27 (4), p.753-762
Main Authors: Shen, Liming, Yang, Aochu, Yao, Pengwei, Sun, Xiaohong, Chen, Cheng, Mo, Cuiping, Shi, Lei, Chen, Youjiao, Liu, Qiong
Format: Article
Language:eng ; dut
Subjects:
Aminoquinolines - pharmacology
Animals
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell growth
Cell Movement
Cell Proliferation - drug effects
Cell Survival - drug effects
Contrast Media - toxicity
Cytoskeleton - drug effects
Cytoskeleton - metabolism
Embryos
Exposure
Fibroblasts
Fibrosis
Gadolinium
Gadolinium - toxicity
Inhibitors
Life Sciences
Medicine/Public Health
Metals
Mice
Microbiology
Migration
Neuropeptides - antagonists & inhibitors
Neuropeptides - metabolism
NIH 3T3 Cells
Pathogenesis
Pathways
Pharmacology/Toxicology
Phosphatidylinositol 3-Kinases
Phosphorylation
Plant Physiology
Protein Processing, Post-Translational
Proto-Oncogene Proteins c-akt - metabolism
Pyrimidines - pharmacology
rac1 GTP-Binding Protein - antagonists & inhibitors
rac1 GTP-Binding Protein - metabolism
Reactive Oxygen Species - metabolism
Rodents
Signal Transduction
Survival
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Summary:Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder disease developed in patients with underlying renal insufficiency following exposure to gadolinium-based contrast agents (GBCAs). Previous studies have demonstrated that GdCl 3 can promote NIH3T3 fibroblast cell proliferation, which provide a new clue to the role of GBCAs in the development of NSF. In the present study, we further clarify the molecular mechanism of Gd-promoted proliferation. The results showed that intervention with the Rac inhibitor NSC23766 abrogated Gd-promoted proliferation. The levels of active Rac1 significantly increased in Gd-treated cells detected by pull-down assays. In addition, the phosphorylation of Akt was significantly elevated in the treatment group, which was blocked by NSC23766. NSC23766 also reduced the migration of NIH3T3 cells enhanced by Gd. Moreover, the F-actin cytoskeleton was strengthened and the mitotic cell numbers was significantly increased after exposure to Gd. These results suggest that Rac and PI3K/Akt signaling pathways, as well as integrin-mediated signal pathway may play important roles in Gd-induced cell proliferation. In addition, under serum-free condition, Gd could decrease ROS accumulation and increase NIH3T3 cell survival.
ISSN:0966-0844
1572-8773
DOI:10.1007/s10534-014-9769-9