Molecular mechanisms of organ regeneration and homeoslasis by injurin/HGF system.

(1)HGF作为有机营养因子的作用：重组HGF可抑制慢性肝损伤所致的肝纤维化、肝硬变和脂肪肝的发生。我们发现HGF在肾和肺的再生中起着肾营养因子和肺营养因子的作用。HGF很可能成为治疗各种器官疾病的新药物，包括肝纤维化/肝硬变、急性肾功能衰竭和肺纤维化。(2)HGF作为一种神经营养因子：HGF促进体外培养的海马神经元存活。重要的是，输注的重组HGF能显著防止大鼠缺血损伤引起的神经元死亡。(3)HGF作为上皮-间充质相互作用的中介：上皮-间充质相互作用是器官发生的关键组织相互作用。HGF在间质组织中表达，而c-Met/HGF受体在肝、肾、肺牙、肢体等发育过程中的上皮组织中表达。HGF作为间质衍生因子支持肝、肾、肺、牙齿、乳腺等多种器官的器官发生。(4)HGF是肿瘤-间质相互作用：肿瘤细胞的恶性表型通过与宿主基质细胞的相互作用来调节。我们发现各种肿瘤细胞产生HGF诱导物(损伤素)，间质来源的HGF促进肿瘤细胞的侵袭。肿瘤细胞与宿主基质细胞之间的物质相互作用介导肿瘤-间质相互作用。(5)肝细胞生长因子诱导物的鉴定：我们从肺组织提取液中分离纯化了S等人肺组织中的肝细胞生长因子，发现它们是IL-1、PDGF和bFGF。相反，我们发现转化生长因子-β和糖皮质激素是HGF表达的负调节因子。

(1) Roles of HGF as an organotrophic factor : Recombinant HGF suppressed the onset of liver fibrosis/cirrhosis and fatty liver caused by chronic hepatic injury. We found that HGF functions as renotrophic and pulmotrophic factor for regeneration of the kidney and lung. HGF may well become a new therapeutic drug for the treatment of various organ diseases, including liver fibrosis/cirrhosis, acute renal failure, and lung fibrosis.(2) HGF as a neurotrophic factor : HGF stimulated survival of hippocampal neurons in vitro. Importantly, the infused recombinant HGF markedly prevented neuronal death caused by ischemic injury in rats.(3) HGF as a mediator in epithelial-mesenchymal interactions : Epithelial-mesenchymal interaction is a critical tissue interaction for organogenesis. HGF is expressed in mesenchymal tissue, while c-Met/HGF receptor in epithelial tissue during development of the liver, kidney, lung tooth, limb, etc. HGF supports organogenesis of various organs, such as the liver, kidney, lung, tooth, mammary gland, as a mesenchymal-derived factor.(4) HGF is tumor-stromal interactions : Malignant phenotypes of tumor cells are regulated through their interactions with host stromal cells. We found that various tumor cells produce HGF-inducer (injurin) and stromal-derived HGF enhanced the invation of tumor cells. Matual interaction between tumor cells and host stromal cells mediate tumor-stromal interactions.(5) Identification of injurin (HGF-inducer) : We purified injurin (s) from lung tissue extract and found that these are IL-1, PDGF,and bFGF.Likewise, we identified tumor-derived injurins as IL-1, PDGF,and bFGF.But mouse mammary tumor cells produced novel HGF-inducer. In contrast, we found that TGF-beta and glucocorticoids are negative regulator of HGF expression.