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

Cardiovascular Diabetology

Original Investigation

Lin Lu¹  Ke Yang¹  Wei Feng Shen¹  Yu Song He¹  Xiao Qun Wang²  Qiu Jing Chen²  Jing Liu² 

[1] Department of Cardiology, Ruijin Hospital, Jiaotong University School of Medicine, 200025, Shanghai, P.R. China;Institute of Cardiovascular Diseases, Jiaotong University School of Medicine, 200025, Shanghai, P.R. China;Institute of Cardiovascular Diseases, Jiaotong University School of Medicine, 200025, Shanghai, P.R. China;

关键词: Reactive Oxygen Species;    Conditioned Medium;    Acute Myocardial Infarction;    Intracellular Reactive Oxygen Species;    Coexpression Network;   

DOI  :  10.1186/1475-2840-9-66

 received in 2010-09-25, accepted in 2010-10-22,  发布年份 2010

来源: Springer

【 摘 要 】

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

【 授权许可】

Unknown   
© Yang et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.