Huang-Joe Wang, Wan-Yu Lo, Li-Jen Lin
School of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan.
Biochemical and biophysical research communications 2013 Jan 18The presence of glycated albumin (GA) is associated with increased diabetic complications. This study investigated the effect of angiotensin-(1-7) on the expression of GA-induced endothelial interleukin-6 (IL-6) in human aortic endothelial cells (HAECs). We also evaluated whether miR-146a is involved in the post-transcriptional regulation of angiotensin-(1-7). HAECs were stimulated with GA with or without angiotensin-(1-7) pretreatment. Inflammatory cytokine screening approach identified that angiotensin-(1-7) (10(-7) M) potently inhibited GA (200 μg/mL)-stimulated endothelial IL-6 expression in conditioned medium. ELISA confirmed this finding. Real-time PCR showed that angiotensin-(1-7) decreased GA-induced intracellular IL-6 mRNA expression and western blotting showed that angiotensin-(1-7) decreased GA-induced intracellular IL-6 protein expression. Bioinformatics' miR target analysis identified homology between miR-146a and the 3'-UTR of the human IL-6 mRNA, suggesting a potential regulation of IL-6 by miR-146a. Treatment with GA decreased endothelial miR-146a expression to 37.2% of the albumin control, while angiotensin-(1-7) increased endothelial miR-146a expression to 1.9-times that of the medium control. Pretreatment with angiotensin-(1-7) inhibited the GA-mediated downregulation of miR-146a to 78.9% of the albumin control levels. Furthermore, the inhibitory effect of angiotensin-(1-7) on IL-6 expression was abolished in GA-treated, miR-146a inhibitor-transfected HAECs. In conclusion, these results suggest that angiotensin-(1-7) exerted an endothelial protective effect through IL-6 downregulation, and miR-146a modulation is involved in this protective effect. Copyright © 2012 Elsevier Inc. All rights reserved.
Huang-Joe Wang, Wan-Yu Lo, Li-Jen Lin. Angiotensin-(1-7) decreases glycated albumin-induced endothelial interleukin-6 expression via modulation of miR-146a. Biochemical and biophysical research communications. 2013 Jan 18;430(3):1157-63
PMID: 23246834
View Full Text