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

我们以前发现，人皮肤成纤维细胞产生少量但可检测到的肝细胞生长因子（HGF）。这一事实表明HGF可能通过其角质形成细胞的生长刺激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激活佛波醇酯、表皮生长因子（EGF）和环腺苷酸升高剂刺激人皮肤成纤维细胞产生HGF。在本研究中，我寻找了其他的HGF生产调节剂，发现抗坏血酸（阿萨）及其稳定的衍生物，如抗坏血酸的2-葡萄糖苷（AA-2G）和2-磷酸盐（AA-2 P），增加HGF的生产。阿萨和AA-2G的作用与上述其他HGF诱导剂的作用是协同的。EGF的作用最明显的是维生素。加入阿萨或AA-2G后，细胞组成性和EGF诱导的HGF基因表达也上调。 ...更多信息 在伤口愈合中起关键作用。局部施用PDGF（其刺激培养物中的间充质细胞的增殖，但不刺激培养的上皮细胞的增殖）至损伤的皮肤促进表皮以及真皮的修复。为了研究HGF是否参与PDGF对伤口愈合的促进作用，检查了PDGF对人皮肤成纤维细胞中HGF产生的作用。PDGF显著增加成纤维细胞分泌HGF。PDGF的作用在10 ng/ml时最大，显示出约6倍的刺激。这种作用小于EGF，但比酸性和碱性成纤维细胞生长因子（aFGF和bFGF）更有效。PDGF的刺激在孵育24小时时是明显的，并且在孵育72小时时变得更加显著。HGF mRNA的稳态水平在加入PDGF后9 h增加，此后随着孵育期的延长进一步升高，直至至少60 h。PDGF诱导的HGF产生被阿萨协同增强，并被TGF-β和地塞米松抑制。这些结果表明PDGF诱导的HGF对PDGF促进伤口愈合的作用有贡献。我们的研究结果，阿萨刺激PDGF诱导的HGF分泌，表明阿萨促进表皮再生过程。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