- Basic Research
- Role of Autophagy in Granulocyte-Colony Stimulating Factor Induced Anti-Apoptotic Effects in Diabetic Cardiomyopathy
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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
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Diabetes Metab J. 2021;45(4):594-605. Published online February 26, 2021
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DOI: https://doi.org/10.4093/dmj.2020.0049
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Graphical Abstract
Abstract
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- 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.
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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 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
- Technology/Device
- Role of MicroRNA-34a in Anti-Apoptotic Effects of Granulocyte-Colony Stimulating Factor in Diabetic Cardiomyopathy
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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
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Diabetes Metab J. 2020;44(1):173-185. Published online April 23, 2019
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DOI: https://doi.org/10.4093/dmj.2018.0211
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Abstract
PDFSupplementary MaterialPubReader
- 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. MethodsRats 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. ResultsG-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. ConclusionOur results indicate that G-CSF might have an anti-apoptotic effect through down-regulation of miR-34a in a diabetic cardiomyopathy rat model.
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Citations
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- 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; 479(7): 1673. 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
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