RRC ID 39266
Author Wu YL, Gohda E, Iwao M, Matsunaga T, Nagao T, Takebe T, Yamamoto I.
Title Stimulation of hepatocyte growth factor production by ascorbic acid and its stable 2-glucoside.
Journal Growth Horm. IGF Res.
Abstract Hepatocyte growth factor (HGF), a cytokine which is generally produced by mesenchymal cells, has mitogenic, motogenic and morphogenic activities in epithelial cells and it also has tumor-suppressing activities. Induction of HGF production may be involved in organ regeneration, wound healing and embryogenesis. We examined the effects of ascorbic acid (AsA), which stimulates the proliferation of fibroblasts, and its stable derivative, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), on HGF production by human skin fibroblasts. Basal HGF secretion was significantly stimulated by more than 0.1 mM AsA or AA-2G. Both vitamins synergistically enhanced HGF secretion stimulated by growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), cholera toxin and other inducers. Induction by EGF or bFGF was most markedly potentiated by the vitamins. HGF production by the KG-1 human leukemia cell line was also augmented by AsA or AA-2G. Another stable AsA derivative, ascorbic acid 2-phosphate (AA-2P) effectively promoted basal and EGF-induced HGF secretion by the fibroblasts, but ascorbic acid 2-sulfate (AA-2S) was much less effective. Intracellular AsA levels increased after the addition of AA-2G and AA-2P as well as AsA, but not after AA-2S. The effect of AA-2G was completely abrogated by the simultaneous addition of castanospermine, an alpha-glucosidase inhibitor, suggesting that the active form of AA-2G is AsA. Constitutive and EGF-induced HGF gene expression was also up-regulated after adding AsA or AA-2G to the cells. These results indicated that AsA acts alone or in synergy with several inducers to stimulate the production and gene expression of HGF in human skin fibroblasts and that the stable AsA derivative AA-2G is as effective as AsA in promoting HGF production.
Volume 8(5)
Pages 421-8
Published 1998-10
DOI 10.1016/s1096-6374(98)80313-4
PII S1096-6374(98)80313-4
PMID 10984304
MeSH Acetylcysteine / pharmacology Antioxidants / pharmacology Ascorbic Acid / analogs & derivatives* Ascorbic Acid / metabolism Ascorbic Acid / pharmacology* Cells, Cultured Child Child, Preschool Drug Synergism Epidermal Growth Factor / pharmacology Female Fibroblasts / drug effects Fibroblasts / metabolism* Gene Expression Regulation / drug effects Glutathione / pharmacology Hepatocyte Growth Factor / genetics Hepatocyte Growth Factor / metabolism* Humans Indolizines / pharmacology Skin / cytology
IF 2.369
Times Cited 15
WOS Category ENDOCRINOLOGY & METABOLISM CELL BIOLOGY
Resource
Human and Animal Cells