Regulation of hepatocyte growth factor production and liver regeneration

肝、肾、肺损伤后肝细胞生长因子（HGF）的产生明显增加。组织中升高的HGF可能具有触发剩余细胞增殖的功能。在这项研究中，细胞因子和其他生理活性化合物对培养的人皮肤成纤维细胞产生HGF的影响进行了研究。此外，环磷酸腺苷（cAMP）升高剂和各种生长因子的汇合培养的细胞显着刺激肝细胞生长因子的生产。经霍乱毒素或毛喉素处理的成纤维细胞分泌HGF的最大量分别是未经处理的细胞的8倍和6倍。8-溴环腺苷酸、二丁酰环腺苷酸、前列腺素E_2和肾上腺素也显著促进HGF分泌。HGF mRNA水平在5和10小时没有显著增加，但在加入这些化合物后15小时或更长时间显著增加。cAMP升高剂和cAMP类似物激活cAMP介导的途径可增强HGF基因表达 ...更多信息 表达和HGF的产生，尽管增加的程度在它们之间是可变的。向融合的人皮肤成纤维细胞中加入EGF、PDGF、bFGF、aFGF和TGF-α也显著刺激HGF产生以及细胞增殖。任何两种EGF、PDGF和bFGF的最佳剂量的所有组合都具有几乎相加的效果。在加入生长因子后，HGF mRNA水平在9小时或更长时间内升高，至少直到60小时。用高剂量PMA预处理，导致PKC下调，并没有减少生长因子对HGF产生的影响，而是增强了它们。因此，生长因子对HGF的诱导可能不依赖于PKC的激活。TGF-β 1和地塞米松抑制cAMP升高剂和生长因子诱导的HGF产生。这些结果表明，肝细胞生长因子在体内的表达可能受到cAMP介导的途径和生长因子。少

Production of hepatocyte growth factor (HGF) markedly increases after injury of liver, kidney and lung. Elevated HGF in the tissues may have a function in triggering proliferation of the remaining cells. In this study, effects of cytokines and other physiologically active compounds on HGF production by human skin fibroblasts in culture were examined. Addition of cyclic AMP (cAMP) -elevating agents and various growth factors to confluent cultures of the cells markedly stimulated HGF production. The maximal secretion of HGF by the fibroblasts exposed to cholera toxin or forskolin was 8 or 6 times that by the untreated cells, respectively. 8-Bromo-cAMP,dibutyryl cAMP, prostaglandin E_2 and epinephrine also remarkably enhanced HGF secretion. HGF mRNA levels did not significantly increase at 5 and 10 h, but increased considerably 15 h or more after the addition of these compounds. Activation of the cAMP-mediated pathway by the cAMP-elevationg agents and the cAMP analogues enhanced HGF gene … More expression and HGF production in human skin fibroblasts isolated from four individuals and in MRC-5 human embryonic lung fibroblasts, although the extent of increase was variable among them. Addition of EGF, PDGF, bFGF, aFGF and TGF-alpha to confluent human skin fibroblasts also markedly stimulated HGF production as well as proliferation of the cells. All combinations of the optimal doses of any two EGF,PDGF and bFGF had nearly additive effects. The HGF mRNA levels were elevated at 9 h or more, at least until 60 h, after addition of the growth factors. Pretreatment with a high dose of PMA, which causes down-regulation in PKC,did not reduce the effects of the growth factors on HGF production, but rather enhanced them. Thus, induction of HGF by the growth factors may occur independently of PKC activation. TGF-beta1 and dexamethasone inhibited HGF production induced by the cAMP-elevating agents and the growth factors. These results suggest that HGF expression in vivo may be regulated by both a cAMP-mediated pathway and the growth factors. Less