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.
Citations
Citations to this article as recorded by
Targeting autophagy in diabetic cardiomyopathy: From molecular mechanisms to pharmacotherapy Jie Li, Yingying Xie, Shuwen Zheng, Haoming He, Zhe Wang, Xuexi Li, Siqi Jiao, Dong Liu, Furong Yang, Hailing Zhao, Ping Li, Yihong Sun Biomedicine & Pharmacotherapy.2024; 175: 116790. CrossRef
Knockout of C1q/tumor necrosis factor-related protein-9 aggravates cardiac fibrosis in diabetic mice by regulating YAP-mediated autophagy Shiyan Ruan, Jun Li, Shengyun Lei, Shaomeng Zhang, Dan Xu, Anju Zuo, Linxi Li, Yuan Guo Frontiers in Pharmacology.2024;[Epub] CrossRef
Ginkgo biloba extract protects against diabetic cardiomyopathy by restoring autophagy via adenosine monophosphateâactivated protein kinase/mammalian target of the rapamycin pathway modulation Xueyao Yang, Xin Zhao, Yanfei Liu, Yue Liu, Libo Liu, Ziyu An, Haoran Xing, Jinfan Tian, Xiantao Song Phytotherapy Research.2023; 37(4): 1377. CrossRef
Perspectives for Forkhead box transcription factors in diabetic cardiomyopathy: Their therapeutic potential and possible effects of salvianolic acids Ronghui Han, Hemeng Huang, Weiyi Xia, Jingjin Liu, Hui Luo, Jing Tang, Zhengyuan Xia Frontiers in Cardiovascular Medicine.2022;[Epub] CrossRef