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Published on: September 15, 2018
[Investigation on the differentially expressed circular RNAs in myocardium of mice with diabetic cardiomyopathy]
1Department of Cardiology, Second Affiliated Hospital of Soochow University, Suzhou 215000, China.
Insights
Researchers identified 63 differentially expressed circular RNAs (circRNAs) in diabetic cardiomyopathy (DCM) mouse hearts. These circRNAs are linked to pathways involved in oxidative stress, fibrosis, and cardiomyocyte death, contributing to DCM progression.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Genomics
Background:
- Diabetic cardiomyopathy (DCM) is a cardiac complication of diabetes.
- Circular RNAs (circRNAs) are emerging as key regulators in various biological processes.
- Understanding circRNA expression in DCM is crucial for elucidating disease mechanisms.
Purpose of the Study:
- To identify differentially expressed circRNAs in the myocardium of DCM mice.
- To analyze the potential biological functions and regulatory networks of these circRNAs.
- To investigate the role of circRNAs in the pathophysiology of DCM.
Main Methods:
- A mouse model of DCM was established using streptozotocin injection.
- High-throughput RNA sequencing was employed to profile circRNA expression in myocardial tissues.
- Bioinformatic analyses, including GO and KEGG pathway analysis, were performed.
- Differential circRNA-microRNA interactions were predicted.
Main Results:
- A total of 63 differentially expressed circRNAs were identified in DCM mouse myocardium.
- RT-qPCR validated the expression patterns of 8 circRNAs (7 up-regulated, 1 down-regulated).
- Up-regulated circRNAs were associated with AMPK signaling and intercellular adhesion pathways.
- Down-regulated circRNAs were linked to cardiomyopathy and contractile fiber components.
Conclusions:
- Novel differentially expressed circRNAs were detected in the myocardium of DCM mice.
- Bioinformatic analysis suggests these circRNAs are involved in oxidative stress, fibrosis, and cardiomyocyte death.
- These circRNAs play a significant role in the pathophysiological processes of DCM.
Abstract:
Objective: To identify the differentially expressed circular RNA (circRNA) in the myocardium of diabetic cardiomyopathy (DCM) mice, and analyze their possible biological functions and related regulatory network. Methods: C57BL/6 mice, aged 8 weeks, and weighing were 21-27 g. Eight mice were selected as the control group and 15 mice were selected as the experimental group. The diabetic mice model was established by intraperitoneal injection of streptozotocin in the experimental group. One week after injection, the fasting blood glucose level of mice was measured, and 12 diabetic mice were included in the final experimental group. All mice were fed for 12 weeks under the same laboratory conditions. The cardiac structure and function were detected by echocardiography. Diabetic mice with the left ventricular ejection fraction less than 60% and the E/A less than 1.6 were selected as DCM group (n=3). Mice in DCM group and control group were then sacrificed under deep anesthesia. RNA was extracted from myocardial tissue. High-throughput RNA sequencing technology was used to sequence and identify the RNA in the myocardial tissue of DCM group and normal control group, and the difference was analyzed by DeSeq2. The analysis results were verified at the tissue level by RT-qPCR, and the differential circRNA were analyzed by GO and KEGG pathway analysis. The differentially expressed circRNA-microRNA(miRNA) interaction was predicted by the miRNA target gene prediction software. Results: A total of 63 differentially expressed circRNAs were found in the myocardium of DCM mice. The results of RT-qPCR showed that the tissue level expression of 8 differentially expressed circRNAs was consistent with the sequencing results, of which 7 were up-regulated and 1 was down-regulated. KEGG pathway analysis showed that the up-regulated circRNAs was mainly related to AMPK signal pathway and intercellular adhesion junction pathway, and the down-regulated circRNA was mainly related to cardiomyopathy. Go analysis showed that the up-regulated circRNA was mainly related to the binding process of ions, proteins, kinases and other factors in terms of molecular function, and was involved in regulating the intracellular structure, especially the composition of organelles in terms of cell components. The functional analysis of molecular function and cell components showed that the up-regulated circRNA were related to the cell component origin, recruitment and tissue, and thus participated in the regulation of cell biological process. The down regulated circRNA was related to catalytic activity in terms of molecular function, protein kinase binding process, transferase and calmodulin activity, and was closely related to the components of contractile fibers and the composition of myofibrils. These differentially expressed circRNAs were also related to biological processes such as lysine peptide modification, sarcomere composition, myofibril assembly, morphological development of myocardial tissue, myocardial hypertrophy and so on. Conclusions: In this study, we detected the novel differentially expressed circRNAs in the myocardium of DCM mice, and bioinformatics analysis confirmed that these circRNAs are related to oxidative stress, fibrosis and death of cardiomyocytes, and finally participate in the pathophysiological process of DCM.
