Cardiac miR-133a overexpression prevents early cardiac fibrosis in diabetes

J Cell Mol Med. 2014 Mar;18(3):415-21. doi: 10.1111/jcmm.12218. Epub 2014 Jan 16.


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.

Keywords: cardiac fibrosis; diabetes; miRNA 133.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensinogen / genetics
  • Angiotensinogen / metabolism
  • Animals
  • Biomarkers / metabolism
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetes Mellitus, Experimental / pathology*
  • E1A-Associated p300 Protein / metabolism
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism
  • Fibrosis
  • Gene Expression Regulation
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Myocardium / metabolism*
  • Myocardium / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Biomarkers
  • Endothelin-1
  • MicroRNAs
  • Mirn133 microRNA, mouse
  • RNA, Messenger
  • Angiotensinogen
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse