title: bFGF Promotes the Migration of Human Dermal Fibroblasts under Diabetic Conditions through Reactive Oxygen Species Production via the PI3K/Akt-Rac1- JNK Pathways.
abstract: Fibroblasts play a pivotal role in the process of cutaneous wound repair, whereas their migratory ability under diabetic conditions is markedly reduced. In this study, we investigated the effect of basic fibroblast growth factor (bFGF) on human dermal fibroblast migration in a high-glucose environment. bFGF significantly increased dermal fibroblast migration by increasing the percentage of fibroblasts with a high polarity index and reorganizing F-actin. A significant increase in intracellular reactive oxygen species (ROS) was observed in dermal fibroblasts under diabetic conditions following bFGF treatment. The blockage of bFGF-induced ROS production by either the ROS scavenger N-acetyl-L-cysteine (NAC) or the NADPH oxidase inhibitor diphenylene iodonium chloride (DPI) almost completely neutralized the increased migration rate of dermal fibroblasts promoted by bFGF. Akt, Rac1 and JNK were rapidly activated by bFGF in dermal fibroblasts, and bFGF-induced ROS production and promoted dermal fibroblast migration were significantly attenuated when suppressed respectively. In addition, bFGF-induced increase in ROS production was indispensable for the activation of focal adhesion kinase (FAK) and paxillin. Therefore, our data suggested that bFGF promotes the migration of human dermal fibroblasts under diabetic conditions through increased ROS production via the PI3K/Akt-Rac1-JNK pathways.
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Hongxue
authors.initials: H
authors.lastname: Shi
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ye
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Pingtao
authors.initials: P
authors.lastname: Cai
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Zhouguang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 2. The First Affiliate Hospital, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Lin
authors.affiliation: 3. Translation Medicine Research Center, Lishui People's Hospital, Wenzhou Medical University, Lishui, 323000, China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Lu
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Hu
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Xinbo
authors.initials: X
authors.lastname: Zhu
authors.affiliation: 2. The First Affiliate Hospital, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Qiqiang
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: 4. Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Chinese PLA General Hospital, Beijing, PR China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: 1. School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035 China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D016764:Cell Polarity / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008856:Microscopy, Fluorescence; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012867:Skin / Q000166:cytology*; D014945:Wound Healing / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C107953:RAC1 protein, human; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016222:Fibroblast Growth Factor 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020830:rac1 GTP-Binding Protein; D005947:Glucose
keywords: bFGF; human dermal fibroblast