Cardiac miR-133a overexpression prevents early cardiac fibrosis in diabetes
Article first published online: 16 JAN 2014
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 18, Issue 3, pages 415–421, March 2014
How to Cite
Chen, S., Puthanveetil, P., Feng, B., Matkovich, S. J., Dorn, G. W. and Chakrabarti, S. (2014), Cardiac miR-133a overexpression prevents early cardiac fibrosis in diabetes. Journal of Cellular and Molecular Medicine, 18: 415–421. doi: 10.1111/jcmm.12218
- Issue published online: 27 FEB 2014
- Article first published online: 16 JAN 2014
- Manuscript Accepted: 27 NOV 2013
- Manuscript Received: 31 JUL 2013
- Heart and Stroke Foundation of Canada
- cardiac fibrosis;
- miRNA 133
Diabetic cardiomyopathy is a cascade of complex events leading to eventual failure of the heart and cardiac fibrosis being considered as one of its major causes. miR-133a is one of the most abundantly expressed microRNAs in the heart. We investigated the role of miR-133a during severe hyperglycaemia. And, our aim was to find out what role miR-133a plays during diabetes-induced cardiac fibrosis. We saw a drastic decrease in miR-133a expression in the hearts of streptozotocin-induced diabetic animals, as measured by RT-qPCR. This decrease was accompanied by an increase in the transcriptional co-activator EP300 mRNA and major markers of fibrosis [transforming growth factor-β1, connective tissue growth factor, fibronectin (FN1) and COL4A1]; in addition, focal cardiac fibrosis assessed by Masson's trichome stain was increased. Interestingly, in diabetic mice with cardiac-specific miR-133aa overexpression, cardiac fibrosis was significantly decreased, as observed by RT-qPCR and immunoblotting of COL4A1, ELISA for FN1 and microscopic examination. Furthermore, Cardiac miR-133a overexpression prevented ERK1/2 and SMAD-2 phosphorylation. These findings show that miR-133a could be a potential therapeutic target for diabetes-induced cardiac fibrosis and related cardiac dysfunction.