Diabetes & Metabolism Journal

Original Articles

Basic Research
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; DOI: https://doi.org/10.4093/dmj.2020.0049

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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.

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: 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; DOI: https://doi.org/10.4093/dmj.2018.0211

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Abstract PDF Supplementary Material PubReader

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.

Citations

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; 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
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

Brief Report

Effect of Granulocyte Colony-Stimulating Factor on the Peripheral Nerves in Streptozotocin-Induced Diabetic Rat: Kyung Ae Lee, Kyung Taek Park, Hea Min Yu, Heung Yong Jin, Hong Sun Baek, Tae Sun Park; Diabetes Metab J. 2013;37(4):286-290. Published online August 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.4.286

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Abstract PDF PubReader

There are controversial reports about the effect of granulocyte colony-stimulating factor (G-CSF) in peripheral nerve protection. Therefore, the present study aimed to investigate the effect of G-CSF on peripheral nerves in streptozotocin (STZ) induced diabetic rats. After STZ or vehicle injection, rats were divided into five groups (n=6) as follows: normal+vehicle, normal+G-CSF (50 µg/kg for 5 days), diabetes mellitus (DM)+vehicle, DM+G-CSF (50 µg/kg for 5 days), and DM+G-CSF extension (50 µg/kg for 5 days and followed by two injections per week up to 24 weeks). Our results showed that the current perception threshold was not significantly different among experimental groups. G-CSF treatment inhibited the loss of cutaneous nerves and gastric mucosal small nerve fibers in morphometric comparison, but statistical significance was not observed. The present results demonstrated that G-CSF has no harmful but minimal beneficial effects with respect to peripheral nerve preservation in diabetic rats.

Citations

Citations to this article as recorded by

Gene expression in the dorsal root ganglion and the cerebrospinal fluid metabolome in polyneuropathy and opioid tolerance in rats
Fredrik H.G. Ahlström, Hanna Viisanen, Leena Karhinen, Vidya Velagapudi, Kim J. Blomqvist, Tuomas O. Lilius, Pekka V. Rauhala, Eija A. Kalso
IBRO Neuroscience Reports.2024; 17: 38. CrossRef
Colony stimulating factors in the nervous system
Violeta Chitu, Fabrizio Biundo, E. Richard Stanley
Seminars in Immunology.2021; 54: 101511. CrossRef
Non-glucose risk factors in the pathogenesis of diabetic peripheral neuropathy
Kyung Ae Lee, Tae Sun Park, Heung Yong Jin
Endocrine.2020; 70(3): 465. CrossRef
Two to Tango: Dialogue between Adaptive and Innate Immunity in Type 1 Diabetes
Lin Sun, Shugang Xi, Guangyu He, Zhuo Li, Xiaokun Gang, Chenglin Sun, Weiying Guo, Guixia Wang
Journal of Diabetes Research.2020; 2020: 1. CrossRef
Transplantation of human mobilized mononuclear cells improved diabetic neuropathy
Se Hee Min, Jung Hee Kim, Yu Mi Kang, Seung Hak Lee, Byung-Mo Oh, Kyou-Sup Han, Meihua Zhang, Hoe Suk Kim, Woo Kyung Moon, Hakmo Lee, Kyong Soo Park, Hye Seung Jung
Journal of Endocrinology.2018; 239(3): 277. CrossRef
Granulocyte-colony stimulating factor as a treatment for diabetic neuropathy in rat
Kyung-Soo Kim, Yi-Sun Song, Jiyong Jin, Jun-Ho Joe, Byung-Im So, Jun-Young Park, Cheng-Hu Fang, Mi Jung Kim, Youl-Hee Cho, Sejin Hwang, Young-Suck Ro, Hyuck Kim, You-Hern Ahn, Hak-Joon Sung, Jung-Joon Sung, Sung-Hye Park, Stuart A. Lipton
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