Diabetes Metab J.  2020 Feb;44(1):173-185. 10.4093/dmj.2018.0211.

Role of MicroRNA-34a in Anti-Apoptotic Effects of Granulocyte-Colony Stimulating Factor in Diabetic Cardiomyopathy

Affiliations
  • 1Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea. kskim@hanyang.ac.kr
  • 2Division of Cardiology, Department of Internal Medicine, Jilin Central Hospital, Jilin University, Jilin, China.
  • 3Department of Laboratory Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
  • 4Division of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
  • 5Department of Thoracic Surgery, Hanyang University Seoul Hospital, Seoul, Korea.

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.

Keyword

Diabetic cardiomyopathies; Granulocyte colony-stimulating factor; MicroRNAs

MeSH Terms

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
Glucose
Granulocyte Colony-Stimulating Factor
Luciferases
MicroRNAs
Streptozocin
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