| Research Abstract |
We found previously that human skin fibroblasts produced a small but detectable amount of hepatocyte growth factor (HGF). This fact indicates the possible involvement of HGF in the tissue formation or regeneration of epidermis through its growth stimulating activity of keratinocytes. We also reported the stimulation of HGF production in human skin fibroblasts by protein kinase C-activating phorbol esters, epidermal growth factor (EGF), and cyclic AMP-elevating agents. Its this study, I searched other regulators of HGF production and found that ascorbic acid (AsA) and its stable derivatives, such as 2-glucoside (AA-2G) and 2-phosphate (AA-2P) of ascorbate, increased HGF production. The effect of AsA and AA-2G was synergistic with those of other HGF inducers described above. Induction by EGF was most markedly potentiated by the vitamins. Constitutive and EGF-induced HGF gene expression was also up-regulated after adding AsA or AA-2G to the cells.
Platelet-derived growth factor (PDGF) may
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have a critical role in wound healing. Local administration of PDGF,which stimulates the proliferation of mesenchymal cells in culture, but not the proliferation of cultured epithelia, to the injured skin promotes the repair of epidermis as well as dermis. In order to investigate whether HGF is involved in the promoting effect of PDGF on wound healing, the effect of PDGF on HGF production in human skin fibroblasts was examined. PDGF markedly augmented HGF secretion by the fibroblasts. The effect of PDGF was maximal at 10 ng/ml, showing about 6-fold stimulation. This effect was less than that of EGF,but more potent than those of acidic and basic fibroblast growth factors (aFGF and bFGF). Stimulation by PDGF was evident at 24 h of incubation and became more striking at 72 h of incubation. The steady-state levels of HGF mRNA increased 9 h after addition of PDGF and was further elevated thereafter with the incubation period until at least 60 h. PDGF-induced HGF production was synergistically potentiated by AsA and inhibited by TGF-beta and dexamethasone. These results suggest the contribution of PDGF-induced HGF to the promoting effect of PDGF on wound healing. Our findings, that AsA stimulated PDGF-induced HGF secretion, suggest that the regenerating process of epidermis is enhanced by AsA. Less
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