title: bFGF-Regulating MAPKs Are Involved in High Glucose-Mediated ROS Production and Delay of Vascular Endothelial Cell Migration.
abstract: High blood sugar is a symptom of diabetes mellitus (DM). Vascular endothelial cells (VECs) directly contact the blood and are damaged when blood sugar levels are high. However, the molecular mechanism underlying this process remains elusive. To analyze the effects of DM on migration, we simulated DM by applying high glucose (HG) to the human VEC. HG delayed cell migration and induced phosphorylation of MAPKs (JNK and ERK). By contrast, in presence of bFGF, cell migration was promoted and MAPK phosphorylation levels were reduced. Furthermore, treatment with JNK and ERK inhibitors rescued HG-mediated delay of cell migration. Molecular and cell biological studies demonstrated that HG increased ROS production, whereas treatment with bFGF or JNK/ERK inhibitors blocked HG-induced ROS accumulation. Addition of MnTMPyP, a ROS scavenger, reduced HG-induced ROS production and accelerated cell migration, suggesting that the influence of HG on bFGF-MAPK signaling causes accumulation of ROS, which in turn regulate cell migration. This is the first study to elucidate the molecular mechanism of HG-mediated VEC migration; these findings could facilitate the development of novel therapies for DM.
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Zhong Xin
authors.initials: ZX
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Wan Hui
authors.initials: WH
authors.lastname: Cai
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Biology, Stanford University, Stanford, 94305-5020, United States of America.
authors.forename: Hong Bo
authors.initials: HB
authors.lastname: Ye
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Yu Ting
authors.initials: YT
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Li Sha
authors.initials: LS
authors.lastname: Chi
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Yuan Meng
authors.initials: YM
authors.lastname: Duan
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Cong Cong
authors.initials: CC
authors.lastname: Sun
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Yuan Hu
authors.initials: YH
authors.lastname: Xuan
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Li Tai
authors.initials: LT
authors.lastname: Jin
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013549:Sweetening Agents / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D013549:Sweetening Agents; D016222:Fibroblast Growth Factor 2; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose