Diabetes Metab J.  2021 Jul;45(4):594-605. 10.4093/dmj.2020.0049.

Role of Autophagy in Granulocyte-Colony Stimulating Factor Induced Anti-Apoptotic Effects in Diabetic Cardiomyopathy

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

Abstract

Background
We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy.
Methods
Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit.
Results
G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro.
Conclusion
Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.

Keyword

Apoptosis; Autophagy; Diabetic cardiomyopathies; Granulocyte colony-stimulating factor; Myocytes, cardiac
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