title: Gadolinium promoted proliferation in mouse embryo fibroblast NIH3T3 cells through Rac and PI3K/Akt signaling pathways.
abstract: 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 GdCl3 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.
authors.affiliation: College of Life Science, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen, 518060, People's Republic of China.
authors.forename: Liming
authors.initials: L
authors.lastname: Shen
authors.forename: Aochu
authors.initials: A
authors.lastname: Yang
authors.forename: Pengwei
authors.initials: P
authors.lastname: Yao
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Sun
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Cuiping
authors.initials: C
authors.lastname: Mo
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Youjiao
authors.initials: Y
authors.lastname: Chen
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000633:toxicity*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D005682:Gadolinium / Q000633:toxicity*; D051379:Mice; D041681:NIH 3T3 Cells; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000634:Aminoquinolines; D003287:Contrast Media; C487513:NSC 23766; D009479:Neuropeptides; D011743:Pyrimidines; C484602:Rac1 protein, mouse; D017382:Reactive Oxygen Species; D005682:Gadolinium; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020830:rac1 GTP-Binding Protein; C038958:gadolinium chloride