The role of the RON receptor tyrosine kinase in a murine model of fulminant hepatic failure

Abstract

as well as colorimetric immunoassays. Results: 1. In LR, maximal Itih4 expression was observed at 30 minutes and 12 hours, predominantly centrizonal in distribution. 2. Itih-4 expression was prominent in early liver development at day 9 and reached a second peak at day 16, being restricted to hepatoblasts, immature hepatncytes and differentiated hepatocytes. 3. A marked increase in Itih-4 labeling was noted in proliferating hepatocytes, but not bile duct cells in liver explant cultures treated with I L-6 (100 units/ml). Itih-4 expression was not altered in explants cultured with TNF alpha. 4. The fluorescence emission spectrum of metal free ITIH-4 showed a maximum at 332 nm with no change on addition of 5 mM Ca. The GST-fusion protein was recovered in the void fraction with no protein binding to the column. Similarly covalent binding of Itih-4 to hyaiuronic acid was not detected. Conclusions: In LR, Itih-4 expression corresponds to that of immediate early genes, such as c-myc, c-los, c-jun, IGFBP-2 and may contribute to the entry of normally quiescent hepetocytes into the early stages of the cell cycle. The markedly high expression of Itih-4 in early liver development and in explants treated with IL-6 suggest a prominent role for Itih-4 in the tissue remodeling that occurs during regenerative and developmental aspects of liver formation.