EXPRESSION AND REGULATION OF KGF AND HGF GENES

角质形成细胞生长因子(KGF)和肝细胞生长因子(HGF) 成纤维细胞来源的有丝分裂原。KGF是一种有效的上皮细胞有丝分裂原 细胞，但对成纤维细胞或其他细胞缺乏相应的活性 非上皮性细胞。肝细胞生长因子是一种广谱有丝分裂原，其活性在 内皮细胞和黑素细胞以及上皮细胞。 结果表明，KGF和HGF在 不同类型的人间质成纤维细胞，如胚胎肺， 包皮、成人皮肤和前列腺成纤维细胞。几个因素的影响 细胞因子对人胚肺HGF和KGF基因表达的诱导作用 对成人皮肤成纤维细胞进行检测。IL-1α、TGFα、bFGFa和 IL-6上调成纤维细胞HGF mRNA水平 肌肉细胞。TGFα、PDGF-BB和IL-1α显著升高 KGF基因的表达水平。IL-1α上调KGF的机制 进一步研究了mRNA的表达。IL-1α增加KGF基因的表达 以时间和剂量依赖的方式表达，通过刺激 KGF基因的转录。这种影响被显著地降低了 抗IL-1抗体。检测到相应水平的KGF蛋白 在IL-1刺激的细胞上清液中。有丝分裂试验表明 存在于IL-1刺激细胞的条件培养液中的KGF可以 支持人类原代角质形成细胞的生长。

Keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are fibroblast-derived mitogens. KGF is a potent mitogen for epithelial cells but lacks corresponding activity on fibroblasts or other nonepithelial cells. HGF is a broad spectrum mitogen with activity on endothelial cells and melanocytes as well as epithelial cells. Results demonstrated that KGF and HGF are widely expressed among different types of human stromal fibroblasts such as embryonic lung, foreskin, adult skin and prostate fibroblasts. The effect of several cytokines in the induction of HGF and KGF mRNA in human embryonic lung and adult skin fibroblasts was examined. IL-1alpha, TGFalpha, bFGF and IL-6 elevated the levels of HGF mRNA in fibroblasts as well as smooth muscle cells. TGFalpha, PDGF-BB and IL-1alpha significantly increased the levels of KGF mRNA. The mechanism by which IL-1alpha elevated KGF mRNA expression was further studied. IL-1alpha increased KGF mRNA expression in time and dose-dependent manners by stimulating the rate of transcription of the KGF gene. This effect was significantly reduced by anti-IL-1 antibodies. Corresponding levels of KGF protein were detected in the supernatant of IL-1-stimulated cells. Mitogenic assays indicated that KGF present in the conditioned medium from IL-1-stimulated cells can support the growth of human primary keratinocytes.