Fibroblast growth factor-10 prevents H2O2-induced cell cycle arrest by regulation of G1 cyclins and cyclin dependent kinases.
We studied the effects of fibroblast growth factor (FGF-10) on H2O2-induced alveolar epithelial cell (AEC) G1 arrest and the role of G1 cyclins. FGF-10 prevented H2O2-induced AEC G1 arrest. FGF-10 induced 2-4-fold increase in cyclin E, cyclin A and CDKs (2,4) alone and in AEC treated with H2O2. H2O2 downregulated cyclin D1; FGF-10 blocked these effects. FGF-10 prevented H2O2-induced upregulation of CDK inhibitor, p21. SiRNAp21 blocked H2O2-induced downregulation of cyclins, CDKs and AEC G1 arrest. Accordingly, we provide first evidence that FGF-10 regulates G1 cyclins and CDKs, and prevents H2O2-induced AEC G1 arrest.
Upadhyay
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Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Drive, Rm H3143, Stanford, CA 94305-5236, USA. upadhyay@stanford.edu
Chang
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W
Wei
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Gao
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M
Rosen
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GD
D002453:Cell Cycle / Q000187:drug effects; D056746:Cyclin G; D056766:Cyclin G1; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D051526:Fibroblast Growth Factor 10 / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
C534702:CCNG1 protein, human; D056746:Cyclin G; D056766:Cyclin G1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D051526:Fibroblast Growth Factor 10; D034741:RNA, Small Interfering; D006861:Hydrogen Peroxide; D018844:Cyclin-Dependent Kinases