The role of hepatocyte growth factor (HGF) in wound healing

我们以前发现，人类皮肤成纤维细胞产生少量但可检测的肝细胞生长因子（HGF）。这一事实表明，HGF可能通过刺激角质形成细胞的生长活性参与表皮的组织形成或再生。我们还报道了蛋白激酶c活化phorbol酯、表皮生长因子（EGF）和环amp升高剂刺激人皮肤成纤维细胞中HGF的产生。在这项研究中，我搜索了其他HGF产生的调节因子，发现抗坏血酸（AsA）及其稳定的衍生物，如抗坏血酸的2-葡萄糖苷（AA-2G）和2-磷酸（AA-2P），增加了HGF的产生。AsA和AA-2G与上述其他HGF诱导剂具有协同作用。维生素对EGF的诱导作用增强最为明显。在细胞中添加AsA或AA-2G后，组成型和egf诱导的HGF基因表达也上调。血小板衍生生长因子（PDGF）可能在伤口愈合中发挥重要作用。局部给予PDGF，刺激培养的间充质细胞的增殖，但不刺激培养的上皮细胞的增殖，损伤皮肤促进表皮和真皮层的修复。为了探讨HGF是否参与了PDGF对伤口愈合的促进作用，我们检测了PDGF对人皮肤成纤维细胞HGF生成的影响。PDGF显著增强成纤维细胞分泌HGF。PDGF在10 ng/ml时作用最大，约有6倍的刺激。这种作用低于EGF，但高于酸性和碱性成纤维细胞生长因子（aFGF和bFGF）。PDGF的刺激作用在孵育24 h时很明显，在孵育72 h时更加明显。添加PDGF 9 h后，HGF mRNA的稳态水平升高，此后随着孵育时间的延长，HGF mRNA的稳态水平进一步升高，直至至少60 h。AsA可协同增强PDGF诱导的HGF生成，tgf - β和地塞米松可抑制PDGF诱导的HGF生成。这些结果提示PDGF诱导的HGF参与了PDGF促进伤口愈合的作用。我们的研究发现，AsA刺激pdgf诱导的HGF分泌，表明AsA促进了表皮的再生过程。少

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 … More 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