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

Shali Chen, Prasanth Puthanveetil, Biao Feng, Scot J. Matkovich, Gerald W. Dorn, Subrata Chakrabarti

Research output: Contribution to journalArticlepeer-review

157 Scopus citations


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.

Original languageEnglish
Pages (from-to)415-421
Number of pages7
JournalJournal of Cellular and Molecular Medicine
Issue number3
StatePublished - Mar 2014


  • Cardiac fibrosis
  • Diabetes
  • MiRNA 133


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