Molecular and cellular biological analyzes of morphogenesis modulated by HGF

1.喂食含乙醇饮食37天的大鼠显示肝脂质显著增加，肝细胞中的脂滴积聚，表明酒精性脂肪肝的发生。在乙醇处理的最后7天给予肝细胞生长因子（HGF）显著降低肝脏脂质至低于HGF处理前的水平.在二甲基亚硝胺诱导的大鼠致死性肝硬化模型中，反复将人HGF基因转染到骨骼肌中诱导了高水平的人和内源性大鼠HGF，以及c-Met/HGR受体的酪氨酸磷酸化。转HGF基因还能抑制肝纤维化和肝细胞凋亡，使肝纤维化完全消退，从而提高重症大鼠的存活率.小鼠是慢性肾病的自发小鼠模型（ICGN品系）， ...更多信息 17周龄时出现肾小管损伤、肾小管萎缩和肾功能不全。在慢性肾病自发小鼠模型（ICGN品系）中，给予HGF 4周（从第14-17周）可预防肾功能不全和纤维化的进展。培养的心肌细胞、心肌内皮细胞及再灌注心肌梗死后存活的边缘区均可产生HGF。与生理盐水处理相比，HGF和HGF基因处理显著减少大鼠再灌注后心肌损伤的梗死面积和凋亡性心肌细胞死亡. HGF对谷氨酸诱导的脑皮质神经元细胞凋亡有保护作用.微泵持续脑室内注射HGF可减轻急性脑缺血模型大脑皮质迟发性神经元细胞死亡.我们以前已经证明了一个包含四个kringle的HGF片段，HGF/NK 4在体内和体外抑制肿瘤的侵袭，并且HGF/NK 4还竞争性地抑制HGF与GB-d1人胆囊癌细胞上的Met/HGF受体的结合，增加植入的GE-d1凋亡细胞的凋亡，并在体内抑制该肿瘤的生长。HGF/NK 4在体内外均能抑制FGF、VEGF和HGF诱导的血管生成，抑制肿瘤生长和血管生成，提示HGF在肿瘤生长和侵袭中具有双重作用。少

1. Rats fed ethanol-containing diets for 37 days showed remarkable increase in hepatic lipids and lipid droplet accumulation in the hepatocytes, indicating the onset of alcholic fatty liver. Administration of hepatocyte growth factor (HGF) for the last seven days of ethanol treatment markedly decreased hepatic lipids to the level lower than that seen before HGF treatment.2. In a rat model of lethal liver cirrhosis produced by dimethylnitrosamine administrations, repeated transfections of the human HGF gene into skeletal muscles induced ahigh plasmalevel of human as well as endogeneous rat HGF, and tyrosine phosphorylation of the c-Met/HGR receptor. Transduction with the HGF gene also inhibited fibrogenesis and hepatocyte appoptosis, and produced the complete resolution of fibrosis in the cirrhotic liver, thereby improving the survival rate of rats with this severe illness.3. The mice, a spontaneous mouse model for chronic renal disease (ICGN strain), progressively developed glomerular … More sclerotic injury, tubular atrophy and renal disfunction until they were 17 wk of age. Administration of HGF for 4-wk-periods(from weeks 14-17) prevented the progression of renal dysfunction and fibrosis in a spontaneous mouse model for chronic renal disease (ICGN strain).4. HGF was produced in cardiomyocytes and cardiac endothelial cells in culture, and in viable border zone of reperfused myocardiac infarction. Administration of HGF and HGF gene markedly decreased infarct area and apoptotic cradiac cell death in rat postreperfusion myocardial injury, compared with saline treatment.5. HGF prevented cerebral corteical neuronal cell induced by glutamate.6. Continuous intra-ventricular administration of HGF by mini-pump attenuated delayed neuronal cell death of cerebral cortex in acute brain ischemic model.7. We have previously demonstrated a four-kringle-containing fragment of HGF, HGF/NK4 inhibits invasion of tumors in vivo, as well as in vitro, and HGF/NK4 also competitively inhibited the binding of HGF to Met/HGF receptor on GB-d1 human gallbladder carcinoma cells, increased apoptosis of implanted GE-d1 apoptotic cell death and inhibited this tumor growth in vivo. In addition to the antagonistic activity against HGF, HGF/NK4 inhibited angiogenesis induced by FGF, VEGF and HGF in vitro and in vivo, and decreased growth size and angiogenesis of tumors, such as Luwis lung cancer cells, suggesting bipotential role of HGF for tumor grwoth and invasion. Less