Abstract 12880: Up-Regulation of Microrna-208b Contributes to Diabetic Myocardial Fibrosis in Mouse
MicroRNAs play important roles in myocardial fibrosis during diabetic cardiomyopathy. The present study aimed to investigate the role of microRNA-208b (miR-208b) in diabetic myocardial fibrosis. Compared to the db/m control mice, Smad3 was activated , fibrosis-related genes expression were significantly up-regulated, and miRNAs were dysregulated in the myocardium of the 16-week-old diabetic db/db mice. miR-208b was confirmed up-regulated in the db/db diabetic myocardium in vivo and in mouse cardiomyocytes and cardiac fibroblasts after treatment with Ang-II, TGF-β and high glucose/glucose oxidase (HG/Go) in vitro, respectively. By using recombinant adenovirus expressing CD63-GFP, rAd-CD63-GFP, we infected neonatal mouse cardiomyocytes with rAd-CD63-GFP and tracked the secreted exosomes with GFP. We found that miR-208b was increased in the secreted exosomes from HG/Go-treated cardiomyocytes, and the exosomes with increased miR-208b could enhance fibrosis associated Col1a1, α-SMA and CTGF expressions in cardiac fibroblasts. Transfection of miR-208b mimic could increase Col1a1, α-SMA and CTGF expression in a dose-dependent manner in cardiac fibroblasts. However, blockage of miR-208b could inhibit fibrosis related genes expression. Mtf2 and Pgrmc1 were verified modulated by miR-208b at post transcriptional level in vitro. Consistently, Mtf2 and Pgrmc1 expressions were decreased in the diabetic myocardium, and knockdown of Mtf2 or Pgrmc1could increase fibrosis related genes expression in cardiac fibroblasts. Smad3 inhibitor, Naringenin, could dramatically inhibit miR-208b expression in cardiac fibroblasts. Taken together, we demonstrated that miR-208b was up-regulated in diabetic fibrotic myocardium, Mtf2 and Pgrmc1 mediated the effect of miR-208b on enhancing Col1a1, α-SMA and CTGF expression in diabetic myocardial fibrosis.
Author Disclosures: Z. Shan: Research Grant; Significant; National Natural Science Foundation of China(No. 81070102, 81270222), Natural Science Foundation of Guangdong Province(No. S2011020005911). L. Guo: None. J. Zhu: None. Q. Lin: None. C. Deng: None. X. Zou: None. Y. Liang: None. W. Zhu: None. X. yu: None. S. Wu: None.
- © 2014 by American Heart Association, Inc.