EXPRESSION AND REGULATION OF KGF AND HGF GENES

角质细胞生长因子（KGF）和肝细胞生长因子（HGF）是 成纤维细胞衍生的有丝分裂原。 KGF是一种有效的上皮细胞有丝分裂原， 细胞，但缺乏对成纤维细胞或其他细胞的相应活性。 非上皮细胞 HGF是一种广谱促分裂原， 内皮细胞和黑素细胞以及上皮细胞。 结果表明，KGF和HGF广泛表达于 不同类型的人基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。 几个影响 细胞因子诱导人胚肺组织中HGF和KGF mRNA的表达 并检查成人皮肤成纤维细胞。 IL-1 α、TGF α、bFGF和 IL-6可使成纤维细胞和平滑肌细胞中HGF mRNA水平升高， 肌肉细胞 TGF α、PDGF-BB和IL-1 α显著升高 KGF mRNA水平。 IL-1 α升高KGF的机制 进一步研究mRNA表达。 IL-1 α增加KGF mRNA 表达的时间和剂量依赖性的方式，通过刺激的速率， KGF基因的转录。 这种影响被大大降低， 抗IL-1抗体。 检测相应的KGF蛋白水平 在IL-1刺激的细胞的上清液中。 有丝分裂试验表明 在IL-1刺激的细胞的条件培养基中存在的KGF可以 支持人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.