Role of MicroRNA-34a in Anti-Apoptotic Effects of Granulocyte-Colony Stimulating Factor in Diabetic Cardiomyopathy
- Author:
In Hwa PARK
1
;
Yi Sun SONG
;
Hyun Woo JOO
;
Guang Yin SHEN
;
Jin Hee SEONG
;
Na Kyoung SHIN
;
Young Jong CHO
;
Yonggu LEE
;
Jeong Hun SHIN
;
Young Hyo LIM
;
Hyuck KIM
;
Kyung Soo KIM
Author Information
- Publication Type:Original Article
- Keywords: Diabetic cardiomyopathies; Granulocyte colony-stimulating factor; MicroRNAs
- MeSH: Animals; Apoptosis; Diabetic Cardiomyopathies; Diet, High-Fat; Down-Regulation; Glucose; Granulocyte Colony-Stimulating Factor; In Vitro Techniques; Luciferases; Lymphoma, B-Cell; MicroRNAs; Models, Animal; Myocardium; Myocytes, Cardiac; Rats; Streptozocin; Transfection
- From:Diabetes & Metabolism Journal 2020;44(1):173-185
- CountryRepublic of Korea
- Language:English
- Abstract: 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.