advanced glycation end products induce chemokinecytokine production via activation of p38 pathway and inhibit proliferation and migration of bone marrow mesenchymal stem cells先进的糖化结束产品诱导chemokinecytokine生产通过p38通路的激活和抑制骨髓间充质干细胞的增殖和迁移.pdfVIP

Yang et al. Cardiovascular Diabetology 2010, 9:66 CARDIO /content/9/1/66 VASCULAR DIABETOLOGY ORIGINAL INVESTIGATION Open Access Advanced glycation end products induce chemokine/cytokine production via activation of p38 pathway and inhibit proliferation and migration of bone marrow mesenchymal stem cells 1,2† 2† 1,2 1,2 2 2 1,2* Ke Yang , Xiao Qun Wang , Yu Song He , Lin Lu , Qiu Jing Chen , Jing Liu , Wei Feng Shen 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 stim