title: Angiotensin-(1-7) decreases glycated albumin-induced endothelial interleukin-6 expression via modulation of miR-146a.
abstract: The 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.
authors.affiliation: School of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan.
authors.forename: Huang-Joe
authors.initials: HJ
authors.lastname: Wang
authors.forename: Wan-Yu
authors.initials: WY
authors.lastname: Lo
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Lin
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019610:Cytoprotection; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D017127:Glycation End Products, Advanced; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D035683:MicroRNAs / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D012709:Serum Albumin / Q000378:metabolism* / Q000633:toxicity; D000093423:Glycated Serum Albumin; D000093242:Interleukin-6 Inhibitors
chemical_list: D000803:Angiotensin I; D017077:Culture Media, Conditioned; D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D035683:MicroRNAs; D010446:Peptide Fragments; D012709:Serum Albumin; D000093423:Glycated Serum Albumin; D000093242:Interleukin-6 Inhibitors; C542542:MIRN146 microRNA, human; C118790:angiotensin I (1-7)