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Diabetes Metab J : Diabetes & Metabolism Journal



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Role of Autophagy in Granulocyte-Colony Stimulating Factor Induced Anti-Apoptotic Effects in Diabetic Cardiomyopathy
Guang-Yin Shen, Jeong-Hun Shin, Yi-Sun Song, Hyun-Woo Joo, In-Hwa Park, Jin-Hee Seong, Na-Kyoung Shin, A-Hyeon Lee, Young Jong Cho, Yonggu Lee, Young-Hyo Lim, Hyuck Kim, Kyung-Soo Kim
Diabetes Metab J. 2021;45(4):594-605.   Published online February 26, 2021
  • 7,641 View
  • 151 Download
  • 3 Web of Science
  • 3 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.
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.
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.
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 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
  • Ginkgo biloba extract protects against diabetic cardiomyopathy by restoring autophagy via adenosine monophosphate‐activated 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
Role of MicroRNA-34a in Anti-Apoptotic Effects of Granulocyte-Colony Stimulating Factor in Diabetic Cardiomyopathy
In-Hwa Park, 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
Diabetes Metab J. 2020;44(1):173-185.   Published online April 23, 2019
  • 5,800 View
  • 75 Download
  • 11 Web of Science
  • 11 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   

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.


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.


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.


Our results indicate that G-CSF might have an anti-apoptotic effect through down-regulation of miR-34a in a diabetic cardiomyopathy rat model.


Citations to this article as recorded by  
  • The study of the mechanism of non-coding RNA regulation of programmed cell death in diabetic cardiomyopathy
    Bingrui Zhang, Hua Wu, Jingwen Zhang, Cong Cong, Lin Zhang
    Molecular and Cellular Biochemistry.2024;[Epub]     CrossRef
  • Non-coding RNAs in the pathophysiology of heart failure with preserved ejection fraction
    Elisabeth A. Jalink, Amber W. Schonk, Reinier A. Boon, Rio P. Juni
    Frontiers in Cardiovascular Medicine.2024;[Epub]     CrossRef
  • The interregulatory circuit between non-coding RNA and apoptotic signaling in diabetic cardiomyopathy
    Hao Wu, Yan Liu, Chunli Liu
    Non-coding RNA Research.2024; 9(4): 1080.     CrossRef
  • Dynamic interplay of microRNA in diseases and therapeutic
    Neha Kargutkar, Priya Hariharan, Anita Nadkarni
    Clinical Genetics.2023; 103(3): 268.     CrossRef
  • LGR5+ Intestinal Stem Cells Display Sex-Dependent Radiosensitivity
    Ryan C. Zitter, Rishi Man Chugh, Payel Bhanja, Bruce F. Kimler, Subhrajit Saha
    Cells.2023; 13(1): 46.     CrossRef
  • Female Mice are More Resistant to the Mixed-Field (67% Neutron + 33% Gamma) Radiation-Induced Injury in Bone Marrow and Small Intestine than Male Mice due to Sustained Increases in G-CSF and the Bcl-2/Bax Ratio and Lower miR-34a and MAPK Activation
    Juliann G. Kiang, Georgetta Cannon, Matthew G. Olson, Joan T. Smith, Marsha N. Anderson, Min Zhai, M. Victoria Umali, Kevin Ho, Connie Ho, Wanchang Cui, Mang Xiao
    Radiation Research.2022;[Epub]     CrossRef
  • Potential Role of Natural Plant Medicine Cyclocarya paliurus in the Treatment of Type 2 Diabetes Mellitus
    Han Wang, Cheng Tang, Zezheng Gao, Yishan Huang, Boxun Zhang, Jiahua Wei, Linhua Zhao, Xiaolin Tong, Yong Xu
    Journal of Diabetes Research.2021; 2021: 1.     CrossRef
  • Ghrelin, a novel therapy, corrects cytokine and NF-κB-AKT-MAPK network and mitigates intestinal injury induced by combined radiation and skin-wound trauma
    Juliann G. Kiang, Joan T. Smith, Georgetta Cannon, Marsha N. Anderson, Connie Ho, Min Zhai, Wanchang Cui, Mang Xiao
    Cell & Bioscience.2020;[Epub]     CrossRef
  • Evaluation of biomarkers in liver following Solanum melongena green calyx administration in diabetic rats
    Shiva Roshankhah, Ahmad Shabanizadeh, Amir Abdolmaleki, Mohammad Reza Gholami, Mohammad Reza Salahshoor
    Journal of Diabetes & Metabolic Disorders.2020; 19(2): 1115.     CrossRef
  • Diabetic cardiomyopathy: definition, diagnosis criteria, treatment directions and prevention of heart failure
    N. A. Koziolova, P. G. Karavaev, A. S. Veklich
    South Russian Journal of Therapeutic Practice.2020; 1(2): 93.     CrossRef
  • The Potential Role of MicroRNA in Diabetic Cardiomyopathy
    Jin Hwa Kim
    Diabetes & Metabolism Journal.2020; 44(1): 54.     CrossRef

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