Role of MicroRNA-34a in Anti-Apoptotic Effects of Granulocyte-Colony Stimulating Factor in Diabetic Cardiomyopathy

• Published in: Diabetes & metabolism journal Vol. 44; no. 1; pp. 173 - 185
• Main Authors: Park, In-Hwa, Song, Yi-Sun, Joo, Hyun-Woo, Shen, Guang-Yin, Seong, Jin-Hee, Shin, Na-Kyoung, Cho, Young Jong, Lee, Yonggu, Shin, Jeong Hun, Lim, Young-Hyo, Kim, Hyuck, Kim, Kyung-Soo
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Diabetes Association / Daehan Dangnyobyeong Hakoe 01.02.2020; Korean Diabetes Association; 대한당뇨병학회
• Subjects: Animal research; Apoptosis; Cardiomyocytes; Cardiomyopathy; Cardiovascular disease; Design of experiments; Diabetes; diabetic cardiomyopathies; Diet; Glucose; granulocyte colony-stimulating factor; Granulocytes; Heart; Insulin resistance; Kinases; MicroRNAs; Original; Pathophysiology; 내과학; South Korea; Seoul South Korea; United States > US; Germany; Granulocyte colony-stimulating factor; Diabetic cardiomyopathies; MicroRNAs
• ISSN: 2233-6079; 2233-6087; 2233-6087
• DOI: 10.4093/dmj.2018.0211

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 . 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.