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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2010

Open Access 01-12-2010 | Original investigation

Advanced glycation end products induce chemokine/cytokine production via activation of p38 pathway and inhibit proliferation and migration of bone marrow mesenchymal stem cells

Authors: Ke Yang, Xiao Qun Wang, Yu Song He, Lin Lu, Qiu Jing Chen, Jing Liu, Wei Feng Shen

Published in: Cardiovascular Diabetology | Issue 1/2010

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Abstract

Background

Advanced glycation products (AGEs), as endogenous inflammatory mediator, compromise the physiological function of mesenchymal stem cells (MSCs). MSCs have a potential role in cell replacement therapy in acute myocardial infarction and ischemic cardiomyopathy. However, mechanisms of AGEs on MSCs are still not unveiled.

Methods

Reactive oxygen species (ROS), genes regulation, cell proliferation and migration have been detected by AGE-BSA stimulated MSCs.

Results

We found that in vitro stimulation with AGE-BSA induced generation of reactive oxygen species (ROS), and inhibited dose-dependently proliferation and migration of MSCs. Microarray and molecular biological assessment displayed an increased expression and secretion of Ccl2, Ccl3, Ccl4 and Il1b in a dose- and time-dependent manner. These chemokines/cytokines of equivalent concentration to those in conditioned medium exerted an inhibitory effect on MSC proliferation and migration after stimulation for 24 h. Transient elevation of phospho-p38 in MSCs upon AGE-BSA stimulation was blocked with p38 inhibitor.

Conclusions

The study indicates that AGE-BSA induces production of chemokines/cytokines in a dose- and time-dependent manner via activation of ROS-p38 mediated pathway. These chemokines/cytokines exert an inhibitory effect on MSC growth and migration, suggesting an amplified dysfunction of MSCs by AGEs.
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Metadata
Title
Advanced glycation end products induce chemokine/cytokine production via activation of p38 pathway and inhibit proliferation and migration of bone marrow mesenchymal stem cells
Authors
Ke Yang
Xiao Qun Wang
Yu Song He
Lin Lu
Qiu Jing Chen
Jing Liu
Wei Feng Shen
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2010
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-9-66

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