FEBS Letters
Volume 584, Issue 1 , Pages 61-66, 4 January 2010

Advanced glycation end products increase endothelial permeability through the RAGE/Rho signaling pathway

Edited by Lukas Huber

First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushyu 807-8555, Japan

Received 17 September 2009; received in revised form 16 November 2009; accepted 17 November 2009. published online 27 November 2009.

Abstract 

Although increased vascular permeability is known to be a major characteristic of diabetic vasculopathy, the precise mechanisms and relevance of advanced glycation end products (AGE) to hyperpermeability of vessels remains unclear. Here, we studied changes in cytoskeletal configuration and the signaling mechanism induced by AGE in human endothelial cells. AGE-BSA stimulation induced Rho activation, intercellular gap formation, prominent actin stress fiber and cell contraction without changing VE-cadherin, and subsequently transendothelial diffusion of FITC-labeled dextran. These processes induced by AGE-BSA were inhibited by either Rho-kinase inhibitor Y27632 or anti-RAGE antibody. We also showed that RhoA and RAGE spontaneously formed a complex. These findings suggest that activation of RAGE/Rho is involved in AGE-BSA-induced hyperpermeability through gap formation and actin reorganization in diabetes.

Structured summary

MINT-7301170: Rhotekin (uniprotkb:Q9BST9) physically interacts (MI:0915) with RhoA (uniprotkb:P61586) by pull down (MI:0096)

MINT-7301204, MINT-7301186: RhoA (uniprotkb:P61586) physically interacts (MI:0915) with RAGE (uniprotkb:Q15109) by anti bait coimmunoprecipitation (MI:0006)

Keywords: AGE, Rho, Permeability, Actin, Endothelial cell, Diabetes mellitus

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PII: S0014-5793(09)00999-5

doi:10.1016/j.febslet.2009.11.082

FEBS Letters
Volume 584, Issue 1 , Pages 61-66, 4 January 2010

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