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.

Plos One
|December 8, 2015
PubMed

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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