Role of MicroRNA-34a in Anti-Apoptotic Effects of Granulocyte-Colony Stimulating Factor in Diabetic Cardiomyopathy.
BACKGROUND
Recent studies have shown that microRNAs (miRNAs) are involved in the process of cardiomyocyte apoptosis. We have previously reported that granulocyte-colony stimulating factor (G-CSF) ameliorated diastolic dysfunction and attenuated cardiomyocyte apoptosis in a rat model of diabetic cardiomyopathy. In this study, we hypothesized a regulatory role of cardiac miRNAs in the mechanism of the anti-apoptotic effect of G-CSF in a diabetic cardiomyopathy rat model.


METHODS
Rats were given a high-fat diet and low-dose streptozotocin injection and then randomly allocated to receive treatment with either G-CSF or saline. H9c2 rat cardiomyocytes were cultured under a high glucose (HG) condition to induce diabetic cardiomyopathy in vitro. We examined the extent of apoptosis, miRNA expression, and miRNA target genes in the myocardium and H9c2 cells.


RESULTS
G-CSF treatment significantly decreased apoptosis and reduced miR-34a expression in diabetic myocardium and H9c2 cells under the HG condition. G-CSF treatment also significantly increased B-cell lymphoma 2 (Bcl-2) protein expression as a target for miR-34a. In addition, transfection with an miR-34a mimic significantly increased apoptosis and decreased Bcl-2 luciferase activity in H9c2 cells.


CONCLUSION
Our results indicate that G-CSF might have an anti-apoptotic effect through down-regulation of miR-34a in a diabetic cardiomyopathy rat model.
['Park|In Hwa|IH|0000-0003-3290-4031', 'Song|Yi Sun|YS|0000-0001-9797-7325', 'Joo|Hyun Woo|HW|', 'Shen|Guang Yin|GY|', 'Seong|Jin Hee|JH|', 'Shin|Na Kyoung|NK|', 'Cho|Young Jong|YJ|', 'Lee|Yonggu|Y|', 'Shin|Jeong Hun|JH|', 'Lim|Young Hyo|YH|', 'Kim|Hyuck|H|', 'Kim|Kyung Soo|KS|0000-0002-0891-1023']
D000818:Animals D017209:Apoptosis D003921:Diabetes Mellitus, Experimental D003924:Diabetes Mellitus, Type 2 D058065:Diabetic Cardiomyopathies D016179:Granulocyte Colony-Stimulating Factor D008297:Male D035683:MicroRNAs D032383:Myocytes, Cardiac D051381:Rats D017207:Rats, Sprague-Dawley D013311:Streptozocin
Diabetic cardiomyopathies MicroRNAs Granulocyte colony-stimulating factor