Identification and Characterization of "Injurin," an Inducer of Expression of the Gene for Hepatocyte Growth Factor

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-05, Vol.89 (9), p.3800-3804
• Main Authors: Matsumoto, Kunio, Tajima, Hisao, Hamanoue, Masahiro, Kohno, Seiho, Kinoshita, Taisei, Nakamura, Toshikazu
• Format: Article
• Language: English
• Subjects: Animals; Carbon Tetrachloride Poisoning - physiopathology; characterization; Cytokines - chemistry; Cytokines - pharmacology; Cytokines - physiology; Epithelial cells; Fibroblasts; gene expression; Gene Expression Regulation - drug effects; Growth Substances - genetics; Hepatectomy; Hepatocyte Growth Factor; Hepatocytes; identification; induction; Injuries; injurin; Ischemia; Kidney - injuries; Kidneys; Liver; Liver - injuries; Lung - physiology; Lungs; Male; Medical research; Messenger RNA; Molecular Weight; Nephrectomy; Physical growth; Physical trauma; Proteins; Rats; Rats, Inbred Strains; Ribonucleic acid; RNA; RNA, Messenger - genetics; Rodents
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.9.3800

The marked and rapid increase of hepatocyte growth factor (HGF) mRNA in the intact lung of rats after partial hepatectomy or unilateral nephrectomy suggests the existence of a humoral factor mediating a signal of injury to distal organs and may induce the expression of HGF gene in these organs. We have now identified a proteinous factor in the sera of rats with injury of liver or kidney that increases HGF mRNA in the intact lung. When the serum of rats with liver insult caused by partial hepatectomy or ischemic treatment was injected i.p. into normal noninjured rats, it induced a marked HGF mRNA expression in the lung of the recipient rats. The addition of serum from rats with various hepatic or renal injuries to MRC-5 human embryonic lung fibroblasts in culture also led to the induction of HGF mRNA expression, so that the production of HGF by MRC-5 cells after treatment with the sera was remarkably increased in the culture medium. However, serum from the normal intact rat induced no HGF production and no HGF mRNA in the lung in vivo and lung fibroblasts in vitro. This factor, which increases HGF production, was purified$>$200-fold from sera of CCl4-treated rats. The factor proved to be an acid- and heat-stable protein with an apparent molecular mass of 10-20 kDa in SDS/PAGE. Its activity markedly increased within 3-6 hr in the plasma of rats after various treatments that injured the liver or kidney. These results suggest that the factor specifically appears in the blood of rats with organ injury and may be involved in organ regeneration through the potential to increase the synthesis of HGF. Since the factor seems to mediate various organ injuries, we named it "injurin."