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

(1) HGF作为器官营养因子的作用：重组HGF抑制慢性肝损伤引起的肝纤维化/肝硬化和脂肪肝的发生。我们发现HGF作为肾和肺再生的肾营养因子和肺营养因子。HGF很有可能成为治疗肝纤维化/肝硬化、急性肾功能衰竭、肺纤维化等多种器官疾病的新型治疗药物。(2) HGF作为神经营养因子：HGF在体外刺激海马神经元的存活。重要的是，注入重组HGF可显著预防大鼠缺血性损伤引起的神经元死亡。(3) HGF在上皮-间充质相互作用中的中介作用：上皮-间充质相互作用是器官发生的重要组织相互作用。在肝、肾、肺、牙、肢体等发育过程中，HGF在间质组织中表达，而c-Met/HGF受体在上皮组织中表达。HGF作为间质源性因子支持各种器官的器官发生，如肝、肾、肺、牙齿、乳腺。(4) HGF是肿瘤-基质相互作用：肿瘤细胞的恶性表型是通过与宿主基质细胞相互作用调控的。我们发现各种肿瘤细胞产生HGF诱导剂（损伤素），基质来源的HGF增强了肿瘤细胞的侵袭。肿瘤细胞与宿主间质细胞之间的相互作用介导肿瘤-间质相互作用。(5)损伤因子（hgf诱导剂）的鉴定：我们从肺组织提取物中纯化损伤因子，发现它们是IL-1、PDGF和bFGF。同样，我们确定了肿瘤源性损伤为IL-1、PDGF和bFGF。而小鼠乳腺肿瘤细胞产生了新的hgf诱导剂。相反，我们发现tgf - 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.