Nowadays, there is limited prevention and treatment for myocardial fibrosis in diabetic cardiomyopathy (DCM). Our study aimed to depict the mechanism of the lncRNA TUG1/miR-145a-5p/Cfl2 axis in DCM and to provide a molecular basis for the study of this disease. Male C57BL/6J mice were intraperitoneally injected with streptozotocin to establish DCM mouse models. The expression levels of lncRNA TUG1, miR-145a-5p, and Cfl2 in myocardial tissues of mice were tested by RT-qPCR or Western blot. Cardiac function was assessed by echocardiography. The contents of Ang-II, TNF-α, and IL-1β were measured using ELISA. The histopathological observation was performed by HE staining and Masson staining. The expression levels of myocardial fibrosis-related genes COL1A1, MMP2, and FN1 were determined by RT-qPCR. In addition, bioinformatics website, RIP assay, pull-down assay, and luciferase activity assay were conducted to verify the relationships of lncRNA TUG1, miR-145a-5p, and Cfl2. In the DCM mouse model, lncRNA TUG1 and Cfl2 expression levels were upregulated and miR-145a-5p expression was downregulated. Downregulation of lncRNA TUG1 improved cardiac function and myocardial fibrosis; decreased COL1A1, MMP2, and FN1 expression levels; as well as TNF-α, IL-1β, and Ang-II contents in myocardial tissues of DCM mice. Upregulation of miR-145a-5p showed the same trend as downregulation of lncRNA TUG1. In addition, upregulating miR-145a-5p reversed the promotion roles of lncRNA TUG1 on myocardial fibrosis in DCM mice, and upregulating Cfl2 compromised the improvement effect of downregulated lncRNA TUG1 on myocardial fibrosis in DCM mice. Mechanistically, there was a binding site between lncRNA TUG1 and miR-145a-5p, and miR-145a-5p had a targeting relationship with Cfl2. This study highlights that lncRNA TUG1 sponges miR-145a-5p to aggravate myocardial fibrosis in DCM mice by promoting Cfl2.
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