Injured Tissue Specific HGF Expression and its Mechanism

我们检测了四氯化碳（CCl_4）处理的日本猴和盐酸（HCl）处理的日本猴各器官中HGF和HGF激活剂的表达。用橄榄油和盐酸分别灌胃单剂量CCl_4制备肝损伤和胃粘膜损伤的日本猴。ELISA法测定人HGF和HGF激活物的HGF和HGF激活物蛋白水平。采用抗HGF单克隆抗体进行Western blot检测组织中HGF的异质性。利用HGF和HGF激活物mrna的cdna进行northern blot分析。ccl_4处理的猴子肝脏中HGF蛋白水平明显升高，脾脏中略有升高。在这些组织中，不仅proHGF增加，成熟HGF也增加。HGF mRNA表达水平升高。而在肾、肺等其他组织中，HGF蛋白和HGF mRNA均无明显升高。HGF激活剂及其mRNA仅在正常和ccl_4处理的猴子肝脏中检测到。此外，仅在ccl_4损伤的肝脏中检测到将proHGF转化为成熟HGF的活性。盐酸处理后，胃黏膜HGF蛋白和HGF mRNA表达明显升高。在hcl损伤的胃粘膜组织中发现了促生HGF和成熟HGF的增加，HGF激活因子mRNA仅在肝脏和ccl_4处理的猴子中检测到。结果表明，HGF存在于肝损伤猴的肝脏中，存在于胃粘膜损伤猴的胃粘膜中，并具有损伤组织特异性。

We examined the expression of HGF and HGF activator in various organs of carbon tetrachloride (CCl_4)-treated Japanese monkeys and hydrochloric acid (HCl)-administered Japanese monkeys. Japanese monkeys with hepatic injury and gastric mucosal injury were prepared by administration of single intragastric dose of CCl_4 in olive oil and HCl, respectively. HGF and HGF activator protein levels were determined using ELISA for human HGF and HGF activator. Heterogeneity of HGF in the tissues were measured by Western blot analysis using anti-HGF monoclonal antibody. HGF and HGF activator mRNAs were analyzed by northern blot analysis using their cDNAs.Marked increase in HGF protein level was observed in the liver of CCl_4-treated monkeys, and its slight increase in the spleen. Not only proHGF but also mature HGF increased in those tissues. Increased expression of HGF mRNA level was also found in those tissues. However, there is no significant increase in HGF protein and HGF mRNA in other tissues including kidney and lung. HGF activator and its mRNA was detected only in the liver of both normal and CCl_4-treated monkeys. In addition, activity which processed proHGF to mature HGF was only detected in the CCl_4-injured liver.HGF protein and HGF mRNA expression in gastric mucosa of HCl-treated monkeys markedly increased. Increase in both proHGF and mature HGF was found in the HCl-injured gastric mucosal tissue and HGF activator mRNA was detected only in the liver as well as CCl_4-treated monkeys.These results suggest that HGF appears in the liver of monkeys with hepatic injury and in the gastric mucosa of monkeys with gastric mucosal injury that is injured-tissue specific.