Dataset Information

Function of BRD4 in the pathogenesis of high glucose?induced cardiac hypertrophy.

ABSTRACT: Diabetic cardiomyopathy is one of the major complications of diabetes, and due to the increasing number of patients with diabetes it is a growing concern. Diabetes?induced cardiomyopathy has a complex pathogenesis and histone deacetylase?mediated epigenetic processes are of prominent importance. The olfactory bromodomain?containing protein 4 (BRD4) is a protein that recognizes and binds acetylated lysine. It has been reported that the high expression of BRD4 is involved in the process of cardiac hypertrophy. The aim of the present study was to investigate the function of BRD4 in the process of high glucose (HG)?induced cardiac hypertrophy, and to clarify whether epigenetic regulation involving BRD4 is an important mechanism. It was revealed that BRD4 expression levels were increased in H9C2 cells following 48 h of HG stimulation. This result was also observed in a diabetic rat model. Furthermore, HG stimulation resulted in the upregulation of the myocardial hypertrophy marker, atrial natriuretic peptide, the cytoskeletal protein ??actin and fibrosis?associated genes including transforming growth factor??, SMAD family member 3, connective tissue growth factor and collagen, type 1, ?1. However, administration of the specific BRD4 inhibitor JQ1 (250 nM) for 48 h reversed this phenomenon. Furthermore, protein kinase B (AKT) phosphorylation was activated by HG stimulation and suppressed by JQ1. In conclusion, BRD4 serves an important role in the pathogenesis of HG?induced cardiomyocyte hypertrophy through the AKT pathway.

SUBMITTER: Wang Q

PROVIDER: S-EPMC6297744 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Function of BRD4 in the pathogenesis of high glucose‑induced cardiac hypertrophy.

Wang Qian Q Sun Yuxin Y Li Tianshu T Liu Lianqin L Zhao Yunxia Y Li Liyuan L Zhang Ling L Meng Yan Y

Molecular medicine reports 20181121 1

Diabetic cardiomyopathy is one of the major complications of diabetes, and due to the increasing number of patients with diabetes it is a growing concern. Diabetes‑induced cardiomyopathy has a complex pathogenesis and histone deacetylase‑mediated epigenetic processes are of prominent importance. The olfactory bromodomain‑containing protein 4 (BRD4) is a protein that recognizes and binds acetylated lysine. It has been reported that the high expression of BRD4 is involved in the process of cardiac ...[more]

PMID: 30483785

Similar Datasets

Project description:Diabetic cardiomyopathy (DCM) is one of the major causes of death in diabetic patients. Its pathogenesis involves inflammation and fibrosis that damages the heart tissue and impairs cardiac function. Interleukin (IL)-17, a pro-inflammatory cytokine that plays an important role in a variety of chronic inflammatory processes can serve as an attractive therapeutic target. Anthocyanin, a water-soluble natural pigment, possesses impressive anti-inflammatory activity. However, its role in DCM is unclear. Hence, we investigated the protective effect of anthocyanin on the cardiovascular complications of diabetes using a mouse type 1 diabetes mellitus model induced by streptozotocin. Cardiac function and structural alterations in diabetic mice were tested by echocardiography, hematoxylin and eosin staining, and Masson trichrome staining. Immunohistochemistry was performed to evaluate the distribution and deposition of IL-17 and collagen I and III from the left ventricular tissues of diabetic mice. Cell viability was measured using the methyl thiazolyl tetrazolium assay. Protein levels of IL-17, tumor necrosis factor α, IL-1β, and IL-6 were determined using enzyme-linked immunosorbent assay. IL-17 and collagen I and III were detected by western blotting and immunofluorescence, and their mRNA levels were quantified using quantitative reverse transcription PCR. We observed that anthocyanin lowered blood glucose, improved cardiac function, and alleviated inflammation and fibrosis in the heart tissue of diabetic mice. Meanwhile, anthocyanin reduced the expression of IL-17 in high-glucose-treated cardiac fibroblasts and exhibited an anti-inflammatory effect. Deposition of collagen I and III was also decreased by anthocyanin, suggesting that anthocyanin contributes to alleviating myocardial fibrosis. In summary, anthocyanin could protect cardiac function and inhibit IL-17-related inflammation and fibrosis, which indicates its therapeutic potential in the treatment of diabetes mellitus-related complications.

Dataset Information

Function of BRD4 in the pathogenesis of high glucose?induced cardiac hypertrophy.

Publications

Function of BRD4 in the pathogenesis of high glucose‑induced cardiac hypertrophy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets