title: Puerarin suppresses high glucose-induced MCP-1 expression via modulating histone methylation in cultured endothelial cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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: Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
authors: Peng
authors: P
authors: Han
authors: 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.
authors: Dehong
authors: D
authors: Gao
authors: Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
authors: Wei
authors: W
authors: Zhang
authors: 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.
authors: Suhuan
authors: S
authors: Liu
authors: 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.
authors: Shuyu
authors: S
authors: Yang
authors: 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.
authors: Xuejun
authors: X
authors: Li
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D044127:Epigenesis, Genetic; D005947:Glucose / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000503:physiopathology; D007529:Isoflavones / Q000494:pharmacology*; D008745:Methylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018932:Chemokine CCL2; D006657:Histones; D007529:Isoflavones; D012333:RNA, Messenger; D005947:Glucose; C033607:puerarin
keywords: Endothelial cell; Histone methylation; Monocyte chemoattractant protein-1; Puerarin