PMID- 25817234 OWN - NLM STAT- MEDLINE DCOM- 20150717 LR - 20150513 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 130 DP - 2015 Jun 1 TI - Puerarin suppresses high glucose-induced MCP-1 expression via modulating histone methylation in cultured endothelial cells. PG - 103-7 LID - S0024-3205(15)00150-2 [pii] LID - 10.1016/j.lfs.2015.02.022 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Han, Peng AU - Han P AD - Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China. FAU - Gao, Dehong AU - Gao D AD - 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. FAU - Zhang, Wei AU - Zhang W AD - Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China. FAU - Liu, Suhuan AU - Liu S AD - 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. FAU - Yang, Shuyu AU - Yang S AD - 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. FAU - Li, Xuejun AU - Li X AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150325 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Chemokine CCL2) RN - 0 (Histones) RN - 0 (Isoflavones) RN - 0 (RNA, Messenger) RN - IY9XDZ35W2 (Glucose) RN - Z9W8997416 (puerarin) SB - IM MH - Cell Line MH - Cells, Cultured MH - Chemokine CCL2/*genetics MH - Chromatin Immunoprecipitation MH - Endothelial Cells/drug effects/metabolism MH - Epigenesis, Genetic MH - Glucose/*metabolism MH - Histones/*metabolism MH - Humans MH - Hyperglycemia/drug therapy/physiopathology MH - Isoflavones/*pharmacology MH - Methylation MH - Promoter Regions, Genetic MH - RNA, Messenger/metabolism MH - Real-Time Polymerase Chain Reaction MH - Up-Regulation/drug effects OTO - NOTNLM OT - Endothelial cell OT - Histone methylation OT - Monocyte chemoattractant protein-1 OT - Puerarin EDAT- 2015/03/31 06:00 MHDA- 2015/07/18 06:00 CRDT- 2015/03/31 06:00 PHST- 2014/09/29 00:00 [received] PHST- 2015/01/10 00:00 [revised] PHST- 2015/02/24 00:00 [accepted] PHST- 2015/03/31 06:00 [entrez] PHST- 2015/03/31 06:00 [pubmed] PHST- 2015/07/18 06:00 [medline] AID - S0024-3205(15)00150-2 [pii] AID - 10.1016/j.lfs.2015.02.022 [doi] PST - ppublish SO - Life Sci. 2015 Jun 1;130:103-7. doi: 10.1016/j.lfs.2015.02.022. Epub 2015 Mar 25.