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Injured Tissue Specific HGF Expression and its Mechanism

损伤组织特异性HGF表达及其机制

基本信息

批准号：
08457171
负责人：
TSUBOUCHI Hirohito
金额：
$ 4.61万
依托单位：
Miyazaki Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

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.

我们检测了四氯化碳(CCl_4)处理的日本猴和盐酸(HCl)处理的日本猴不同器官中HGF和HGF激活物的表达。用日本猕猴肝损伤模型和胃黏膜损伤模型，分别用橄榄油和盐酸单次灌胃CCl4。采用双抗体夹心法测定人肝细胞生长因子和肝细胞生长因子激活物蛋白水平。用抗HGF单抗进行Western印迹分析，检测组织中HGF的异质性。对HGF和HGF激活物的cDNAs进行Northern印迹分析，发现CCl4处理的猕猴肝脏中HGF蛋白水平显著升高，脾中HGF蛋白水平略有增加。这些组织中不仅有proHGF的表达，也有成熟HGF的表达。HGF基因在上述组织中的表达水平也明显升高。而在肾、肺等其他组织中，HGF蛋白和HGF mRNA的表达没有显著增加。HGF激活物及其mRNA仅在正常和CCl_4处理的猕猴肝脏中检测到。此外，只有在CCl_4损伤的肝脏中才能检测到将proHGF转化为成熟HGF的活性，HGF蛋白和HGF mRNA在胃黏膜中的表达显著增加。结果表明，HGF在肝损伤猴的肝脏和胃粘膜损伤的胃黏膜组织中均有表达，且HGF激活子mRNA的表达具有组织特异性。