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bFGF-Regulating MAPKs Are Involved in High Glucose-Mediated ROS Production and Delay of Vascular Endothelial Cell
Zhong Xin Zhu1, Wan Hui Cai1, Tao Wang1
1School of Pharmaceutical Sciences, Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325000, China.
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.
Insights
High glucose levels in diabetes mellitus impair vascular endothelial cell migration by increasing ROS production via MAPK signaling. Fibroblast growth factor and MAPK inhibitors restore normal cell function.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Cellular Biology
Background:
- Diabetes mellitus (DM) is characterized by high blood sugar.
- High glucose damages vascular endothelial cells (VECs) that line blood vessels.
- The precise molecular mechanisms of this damage are not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms by which high glucose affects VEC migration.
- To explore the role of MAPK signaling and reactive oxygen species (ROS) in high glucose-induced VEC dysfunction.
Main Methods:
- Human VECs were exposed to high glucose (HG) conditions to simulate DM.
- Cell migration assays were performed.
- MAPK phosphorylation (JNK and ERK) and ROS production were measured.
- The effects of bFGF, MAPK inhibitors, and a ROS scavenger (MnTMPyP) were evaluated.
Main Results:
- HG significantly delayed VEC migration and increased ROS production.
- HG induced phosphorylation of JNK and ERK MAPKs.
- Basic fibroblast growth factor (bFGF) promoted migration and reduced MAPK phosphorylation and ROS levels.
- Inhibiting JNK and ERK, or scavenging ROS, rescued the HG-induced delay in cell migration.
Conclusions:
- High glucose impairs VEC migration through a mechanism involving increased ROS production mediated by MAPK signaling.
- bFGF and MAPK inhibitors counteract these detrimental effects.
- These findings offer insights into potential therapeutic targets for diabetic vascular complications.
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