TY - JOUR
T1 - Cardiac miR-133a overexpression prevents early cardiac fibrosis in diabetes
AU - Chen, Shali
AU - Puthanveetil, Prasanth
AU - Feng, Biao
AU - Matkovich, Scot J.
AU - Dorn, Gerald W.
AU - Chakrabarti, Subrata
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
KW - Cardiac fibrosis
KW - Diabetes
KW - MiRNA 133
UR - http://www.scopus.com/inward/record.url?scp=84894577814&partnerID=8YFLogxK
U2 - 10.1111/jcmm.12218
DO - 10.1111/jcmm.12218
M3 - Article
C2 - 24428157
AN - SCOPUS:84894577814
SN - 1582-1838
VL - 18
SP - 415
EP - 421
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
IS - 3
ER -