Peng Han1, Dehong Gao2, Wei Zhang1, Suhuan Liu3, Shuyu Yang4, Xuejun Li5. 1. Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China. 2. Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China; Department of Pathology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China. 3. Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China; Central Laboratory, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China. 4. Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China; Division of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China. Electronic address: xmyangshuyu@126.com. 5. Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China; Division of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China. Electronic address: xmlixuejun@163.com.
Abstract
AIMS: Hyperglycemia is commonly associated with microcirculation dysfunction. The purpose of the present study was to investigate the epigenetic mechanism involved in the repression of monocyte chemoattractant protein-1 (MCP-1) expression by puerarin under high glucose (25mM) condition. MAIN METHODS: MCP-1 gene expression was measured by Real-Time quantitative Polymerase Chain Reaction (RT-qPCR), the histone 3 lysine 4 methylation (H3K4me) and lysine 9 methylation (H3K9me) were evaluated using chromatin immunoprecipitation assay. KEY FINDINGS: Puerarin significantly inhibited high glucose-induced upregulation of H3K4 di- and tri-methylation (H3K4me2/3) on the MCP-1 gene promotor. Additionally, the enrichment of H3K4 histone methyltransferases including MLL, menin and SET7 on the MCP-1 promotor was increased, while the demethylase LSD1 was decreased in EA.hy926 cells following exposure to high glucose. The changes of the above enzymes were reversed by puerarin treatment. The mRNA expression of MCP-1 was increased by LSD1 blockage, while was decreased by MLL3 blockage. SIGNIFICANCE: Our findings suggested that puerarin plays a critical role in transcriptional repression of high glucose-induced MCP-1 gene expression, at least in part due to alteration of H3K4me2/3 methylation, thus possesses a therapeutic potential in diabetes-induced vascular injuries.
AIMS: Hyperglycemia is commonly associated with microcirculation dysfunction. The purpose of the present study was to investigate the epigenetic mechanism involved in the repression of monocyte chemoattractant protein-1 (MCP-1) expression by puerarin under high glucose (25mM) condition. MAIN METHODS:MCP-1 gene expression was measured by Real-Time quantitative Polymerase Chain Reaction (RT-qPCR), the histone 3 lysine 4 methylation (H3K4me) and lysine 9 methylation (H3K9me) were evaluated using chromatin immunoprecipitation assay. KEY FINDINGS:Puerarin significantly inhibited high glucose-induced upregulation of H3K4 di- and tri-methylation (H3K4me2/3) on the MCP-1 gene promotor. Additionally, the enrichment of H3K4 histone methyltransferases including MLL, menin and SET7 on the MCP-1 promotor was increased, while the demethylase LSD1 was decreased in EA.hy926 cells following exposure to high glucose. The changes of the above enzymes were reversed by puerarin treatment. The mRNA expression of MCP-1 was increased by LSD1 blockage, while was decreased by MLL3 blockage. SIGNIFICANCE: Our findings suggested that puerarin plays a critical role in transcriptional repression of high glucose-induced MCP-1 gene expression, at least in part due to alteration of H3K4me2/3 methylation, thus possesses a therapeutic potential in diabetes-induced vascular injuries.
Authors: Hong Ding; Wen Chao Lu; Jun Chi Hu; Yu-Chih Liu; Chen Hua Zhang; Fu Lin Lian; Nai Xia Zhang; Fan Wang Meng; Cheng Luo; Kai Xian Chen Journal: Molecules Date: 2018-03-02 Impact factor: 4.411