Formononetin accelerates wound repair by the regulation of early growth response factor-1 transcription factor through the phosphorylation of the ERK and p38 MAPK pathways
Formononetin accelerates wound repair by the regulation of early growth response factor-1 transcription factor through the phosphorylation of the ERK and p38 MAPK pathways
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DOI：
10.1016/j.intimp.2010.10.003
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发表时间：
2011-01-01
影响因子：
5.6
通讯作者：
Lee, Jae-Dong
中科院分区：
文献类型：
--
作者：
Huh, Jeong-Eun;Nam, Dong-Woo;Lee, Jae-Dong
芒柄花素是黄芪根中的一种植物雌激素，在补充医学和替代医学中用作血液增强剂和改善血液微循环。本研究探讨芒柄花素对创面早期生长反应因子-1(Egr-1)和促进创面愈合的生长因子表达的影响。芒柄花素可显著增加人脐静脉内皮细胞转化生长因子-β1、血管内皮生长因子、血小板衍生生长因子、碱性成纤维细胞生长因子等生长因子的表达。与重组血管内皮细胞(125)相比，Formononetin还可使Egr-1转录因子的表达分别增加3.2倍和10.5倍。芒柄花素介导的内皮细胞增殖增加12%-43%，并恢复损伤内皮细胞的迁移。在体外血管生成试验中，芒柄花素产生的毛细血管萌发面积比重组血管内皮生长因子(125)产生的更大。在Foronectin存在的情况下，HUVEC的细胞增殖和迁移也比VEGF更强(125)。Western印迹分析显示芒柄花素可诱导细胞外信号调节蛋白激酶(ERK)的磷酸化，而对p38丝裂原活化蛋白激酶(MAPK)的磷酸化有轻微的抑制作用。芒柄花素介导的Egr-1持续激活可被ERK抑制剂PD98059和p38抑制剂SB203580抑制。PD98059抑制芒柄花素诱导的内皮细胞增殖和修复，SB203580促进细胞增殖和创面愈合。在创伤动物模型中，Formononetin最早在术后3d加速创面闭合率，并持续观察到10d。这些数据表明，芒柄花素通过调节ERK1/2和p38 MAPK通路促进内皮修复和伤口愈合，涉及Egr-1转录因子的过度表达。皇冠版权所有(C)2010由爱思唯尔出版。保留所有权利。
Formononetin, a phytoestrogen from the root of Astragalus membranaceus, is used as a blood enhancer and to improve blood microcirculation in complementary and alternative medicine. The present study investigated the influence of formononetin on the expression of early growth response factor-1 (Egr-1) and growth factors contributing to wound healing. Formononetin significantly increased growth factors such as transforming growth factor-beta 1 (TGF-beta 1), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) in human umbilical vein endothelial cells (HUVECs). Formononetin also increased the expression of Egr-1 transcription factor by 3.2- and 10.5-fold, compared with recombinant VEGF(125) in HUVECs. The formononetin-mediated 12%-43% increase induced endothelial cell proliferation and recovered the migration of wounded HUVECs. In an ex vivo angiogenesis assay, formononetin produced a larger capillary sprouting area than produced using recombinant VEGF(125). Cell proliferation and migration of HUVECs were also greater in the presence of formonectin than VEGF(125). Western blot analysis of scratch-wounded confluent HUVECs showed that formononetin induced the phosphorylation of extracellular signal-regulated kinase (ERK) and slightly inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The formononetin-mediated sustained activation of Egr-1 was suppressed by the ERK inhibitor PD98059 and the p38 inhibitor SB203580. PD98059 inhibited the formononetin-induced endothelial proliferation and repair in scratch-wounded HUVECs, SB203580 increased the cell proliferation and wound healing. Formononetin accelerate wound closure rate as early as day 3 after surgery and consistently observed until day 10 after in wound animal model. These data suggest that formononetin promotes endothelial repair and wound healing in a process involving the over-expression of Egr-1 transcription factor through the regulation of the ERK1/2 and p38 MAPK pathways. Crown Copyright (C) 2010 Published by Elsevier B.V. All rights reserved.