Injured Tissue Specific HGF Expression and its Mechanism

点击翻译按钮获取中文摘要

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.