INDUCTION OF HGF AFTER LIVER INJURIES AND IDENTIFICATION OF INDUCER FOR HGF

肝细胞生长因子（HGF）可诱导包括成熟肝细胞在内的各种上皮细胞的有丝分裂、运动发生和形态发生，被认为是肝再生的肝营养因子。我们研究了肝脏和肾脏各种损伤后HGF的诱导，并确定了HGF的诱导剂。在各种肝损伤（肝炎、部分肝切除等）或肾损伤（单侧肾切除术、缺血、hgcl_2给药等）发生后，不仅损伤脏器中HGF的表达迅速而显著地被诱导，而且远端完整脏器（如肺、脾）中HGF的表达也迅速而显著地被诱导。因此，HGF似乎通过旁分泌和内啡肽机制作为肝和肾再生的肝营养因子和嗜肾因子。我们在器官损伤大鼠血清中发现了HGF的诱导因子，并将其命名为“损伤因子”。从大鼠血清中部分纯化出损伤蛋白，发现其是一种酸热稳定的蛋白质因子，Mr为10-30kDa。除了损伤外，白细胞介素-1（IL-1）和肝素也增加了培养成纤维细胞中HGF的合成，而转化生长因子- β 1（tgf - β 1）和糖皮质激素抑制HGF的表达，作为HGF的负调节因子。损伤素、IL-1和肝素可在肝或肾损伤后迅速分泌并诱导HGF的表达。另一方面，tgf - β 1可能通过抑制HGF表达而参与器官再生的终止。HGF及其调节因子不仅在器官再生中发挥重要作用，而且在器官发生和体内平衡中也发挥着重要作用。

Hepatocyte growth factor(HGF)induces mitogenesis,motogenesis and morphogenesis of various epithelial cells,including mature hepatocytes and has been considered to act as a hepatotrophic factor for liver regeneration.We have studied induction of HGF following various injuries in the liver and kidney and identified inducers for HGF.Expression of HGF was rapidly and markedly induced following onset of various liver injuries(hepatitis,partial hepatectomy,etc.) or renal injuries(unilateral nephrectomy,ischemia,HgCl_2-administration,etc.)not only in injured organ but also in distant intact organs such as lung and spleen.Thus HGF seems to act as hepatotrophic and renotropic factor for regeneration of liver and kidney through a paracrine and an endorine mechanisms.We next found the presence of an inducer for expression of HGF in serum of rat with organ injury and named the factor "injurin".Injurin was partially purified from the serum of rats and was found to be acid-and heat-stable proteious factor with Mr of 10-30kDa.In addition to injurin,interleukin-1(IL-1)and heparin also increased HGF synthesis in cultured fibroblasts,whereas transforming growth factor-beta1(TGF-beta1)and glucocorticoids suppressed expression of HGF,acting as negative regulators for HGF.Injurin,IL-1,and heparin may be rapidly secreted following hepatic or renal injuries and induce expression of HGF.On the other hand TGF-beta1 may be involved in the termination of organ regeneration through its potential to suppress HGF expression.HGF and its regulators may have important roles not only for organ regeneration,but also for organogenesis and homeostasis of organs.