International immunopharmacology, 2011, Vol.11 (1), p.46-54
2011
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- Autor(en) / Beteiligte
- Titel
- 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
- Ist Teil von
- International immunopharmacology, 2011, Vol.11 (1), p.46-54
- Ort / Verlag
- Kidlington: Elsevier B.V
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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-β1), 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1567-5769eISSN: 1878-1705DOI: 10.1016/j.intimp.2010.10.003Titel-ID: cdi_proquest_miscellaneous_864955689
- Format
- –
- Schlagworte
- Animals, Astragalus, Biological and medical sciences, Cell Line, Cell Proliferation - drug effects, Disease Models, Animal, Early growth response factor (Egr)-1, Early Growth Response Protein 1 - biosynthesis, Early Growth Response Protein 1 - genetics, Endothelial Cells - drug effects, Endothelial Cells - enzymology, Endothelial Cells - immunology, Extracellular signal-regulated kinase (ERK) 1/2, Extracellular Signal-Regulated MAP Kinases - metabolism, Formononetin, Humans, Isoflavones - administration & dosage, Isoflavones - pharmacology, Isoflavones - therapeutic use, Medical sciences, Mice, Mice, Nude, Molecular Structure, Muscle, Skeletal - blood supply, Muscle, Skeletal - drug effects, Neovascularization, Physiologic - drug effects, p38 mitogen-activated protein kinase, p38 Mitogen-Activated Protein Kinases - metabolism, Pharmacology. Drug treatments, Phosphorylation, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Skin - blood supply, Skin - injuries, Skin - pathology, Wound Healing - drug effects, Wound repair, Wounds, Penetrating - drug therapy, Wounds, Penetrating - enzymology, Wounds, Penetrating - immunology