title: Acidic Fibroblast Growth Factor Promotes Endothelial Progenitor Cells Function via Akt/FOXO3a Pathway.
abstract: Acidic fibroblast growth factor (FGF1) has been suggested to enhance the functional activities of endothelial progenitor cells (EPCs). The Forkhead homeobox type O transcription factors (FOXOs), a key substrate of the survival kinase Akt, play important roles in regulation of various cellular processes. We previously have shown that FOXO3a is the main subtype of FOXOs expressed in EPCs. Here, we aim to determine whether FGF1 promotes EPC function through Akt/FOXO3a pathway. Human peripheral blood derived EPCs were transduced with adenoviral vectors either expressing a non-phosphorylable, constitutively active triple mutant of FOXO3a (Ad-TM-FOXO3a) or a GFP control (Ad-GFP). FGF1 treatment improved functional activities of Ad-GFP transduced EPCs, including cell viability, proliferation, antiapoptosis, migration and tube formation, whereas these beneficial effects disappeared by Akt inhibitor pretreatment. Moreover, EPC function was declined by Ad-TM-FOXO3a transduction and failed to be attenuated even with FGF1 treatment. FGF1 upregulated phosphorylation levels of Akt and FOXO3a in Ad-GFP transduced EPCs, which were repressed by Akt inhibitor pretreatment. However, FGF1 failed to recover Ad-TM-FOXO3a transduced EPCs from dysfunction. These data indicate that FGF1 promoting EPC function is at least in part mediated through Akt/FOXO3a pathway. Our study may provide novel ideas for enhancing EPC angiogenic ability and optimizing EPC transplantation therapy in the future.
authors.affiliation: Department of Geriatrics, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Geriatrics, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Geriatrics, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Sang
authors.affiliation: Department of Geriatrics, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Geriatrics, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015290:Second Messenger Systems
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D016220:Fibroblast Growth Factor 1; D051057:Proto-Oncogene Proteins c-akt