scholarly journals Advanced Glycation End Products Induce Endothelial-to-Mesenchymal Transition via Downregulating Sirt 1 and Upregulating TGF-βin Human Endothelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Wei He ◽  
Jian Zhang ◽  
Tian-yi Gan ◽  
Guo-jun Xu ◽  
Bao-peng Tang

In the present study, we examined the advanced glycation end products- (AGEs-) induced endothelial-to-mesenchymal transition (EndMT) in human umbilical vein endothelial cells (HUVECs). Results demonstrated that AGE-BSAs significantly reduced the cluster of differentiation 31 (CD 31) expression, whereas they promoted the expression of fibroblast-specific protein-1 (FSP-1),α-smooth muscle antibody (α-SMA), and collagen I at both mRNA and protein levels in HUVECs. And the AGE-BSAs also promoted the receptors for AGEs (RAGEs) and receptor I for TGF-β(TGFR I) markedly with a dose dependence, whereas the Sirt 1 was significantly downregulated by the AGE-BSA at both mRNA and protein levels. Moreover, the Sirt 1 activity manipulation with its activator, resveratrol (RSV), or its inhibitor, EX527, markedly inhibited or ameliorated the AGE-mediated TGF-βupregulation. And the manipulated Sirt 1 activity positively regulated the AGE-induced CD31, whereas it negatively regulated the AGE-induced FSP-1. Thus, Sirt 1 was confirmed to regulate the AGE-induced EndMT via TGF-β. In summary, we found that AGE-BSA induced EndMT in HUVECs via upregulating TGF-βand downregulating Sirt 1, which also negatively regulated TGF-βin the cell. This study implied the EndMT probably as an important mechanism of AGE-induced cardiovascular injury.

2007 ◽  
Vol 35 (5) ◽  
pp. 709-715 ◽  
Author(s):  
L Gao ◽  
L Kang ◽  
Q Chen ◽  
C Chen ◽  
B Xu ◽  
...  

The aim of this study was to investigate the effects of advanced glycation end products (AGEs) on the expression and activity of matrix metalloproteinases-2 (MMP-2) in human umbilical vein endothelial cells (HUVECs). Cultured HUVECs were incubated with various concentrations of AGEs-modified albumin or unmodified albumin for different time periods. Protein and gene expression of MMP-2 and the receptor for AGEs (RAGE) were measured by Western blot and reverse transcription-polymerase chain reaction, respectively. The activity of MMP-2 in the conditioned medium was measured by gelatin zymography. The AGE-modified albumin inhibited MMP-2 but increased RAGE protein and gene expression in HUVECs in a concentration- and time-dependent manner. An inhibition of MMP-2 activity was also detected in the conditioned medium of HUVECs incubated with AGEs-modified albumin. In conclusion, AGEs inhibited the expression and activity of MMP-2 in HUVECs; this may be mediated through upregulation of RAGE.


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