title: Herbal formula HMC05 prevents human aortic smooth muscle cell migration and proliferation by inhibiting the ERK1/2 MAPK signaling cascade.
abstract: HMC05 is a formulation derived from eight medicinal herbs, and prevents neointima formation by inhibition of the mitogen-activated protein kinase (MAPK) pathway with induction of heat shock protein 27 expression. In this study, we investigated the influence of HMC05 regulation on the MAPK/extracellular signal-regulated kinase (ERK) 1/2 signaling cascade in the inhibition of the migration and proliferation of human aortic smooth muscle cells (HASMCs). The inhibitory effects of HMC05 (25, 50, and 100 μg/ml) on tumor necrosis factor-alpha (TNF-α; 0 or 100 ng/ml)-induced HASMC migration and proliferation were investigated by wound migration and proliferation assays, Western blotting and reverse transcription-polymerase chain reaction. HMC05 completely inhibited TNF-α-induced HASMC migration and proliferation. HMC05 prevented TNF-α receptor 1-mediated phosphorylation of signal transduction molecules involved in MAPK signaling cascades such as MEK1/2, ERK1/2, Elk-1 transcription factor and p90 kDa ribosomal S6 kinase. The expression of matrix metalloproteinase, a modulator of vascular smooth muscle cell proliferation and migration, was inhibited by HMCO5 treatment, as was TNF-α-induced mRNA expression of intracellular adhesion molecule 1 and vascular cell adhesion molecule 1. HMC05 disruption of the MEK/ERK/Elk-1 and p90RSK pathways prevents HASMC migration and proliferation.
authors.affiliation: Department of Physiology, College of Oriental Medicine, Dongguk University, Gyeongju 780-714, Republic of Korea.
authors.forename: Yun Hwan
authors.initials: YH
authors.lastname: Kang
authors.forename: In Jun
authors.initials: IJ
authors.lastname: Yang
authors.forename: Heung Mook
authors.initials: HM
authors.lastname: Shin
mesh_terms: D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology; D010936:Plant Extracts / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C494112:ELK1 protein, human; C526235:HMCO5 herbal extract; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; C506235:TNFRSF1A protein, human; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D050807:ets-Domain Protein Elk-1; D018799:Intercellular Adhesion Molecule-1; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020780:Matrix Metalloproteinase 9