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Role of Src in Vascular Hyperpermeability Induced by Advanced Glycation End Products

Weijin Zhang1, Qiulin Xu2,3, Jie Wu1

  • 1Department of Pathophysiology, Key Laboratory for Shock and Microcirculation Research of Guangdong Province, Southern Medical University, Guangzhou 510515, China.

Scientific Reports
|September 19, 2015
PubMed

Insights

Advanced glycation end products (AGEs) increase vascular permeability by activating Src kinase. This pathway involves moesin, VE-cadherin, and FAK, contributing to diabetic vasculopathy.

Area of Science:

  • Endothelial Biology
  • Molecular Medicine
  • Diabetic Complications

Background:

  • Microvascular barrier disruption is a hallmark of diabetic vasculopathy.
  • Advanced glycation end products (AGEs) are implicated in diabetes-associated vascular damage.

Purpose of the Study:

  • To investigate the role of Src kinase in AGE-induced microvascular hyperpermeability.
  • To elucidate the association between Src, moesin, VE-cadherin, and focal adhesion kinase (FAK) in this process.

Main Methods:

  • Utilized human umbilical vein endothelial cells (HUVECs) and pulmonary microvascular endothelial cells (PMVECs).
  • Employed Src overexpression, inhibition (siRNA, PP2, dominant-negative mutant), and RAGE-knockout mice models.
  • Assessed vascular permeability, F-actin rearrangement, protein phosphorylation, and molecular interactions.

Main Results:

  • AGEs induced Src phosphorylation and increased endothelial permeability.
  • Src activation mimicked AGE effects, while Src inhibition abolished them.
  • RAGE deficiency attenuated AGE-induced Src phosphorylation and barrier dysfunction.
  • Src activation led to moesin phosphorylation, VE-cadherin dissociation, and FAK interaction.

Conclusions:

  • Src kinase is a critical mediator of AGE-induced microvascular hyperpermeability.
  • Src regulates endothelial barrier function through phosphorylation of moesin, VE-cadherin, and FAK.
  • Targeting Src may offer a therapeutic strategy for diabetic vasculopathy.

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