N terminal-DDR1, A serum prognostic marker for liver fibrosis

Abstract

Introduction: Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and transmits signals from various collagens in epithelial cells, which including liver cells. However, how DDR1-dependent signaling is regulated has not been understood. It was report that collagen binding induces ectodomain shedding of DDR1. As we know, organ fibrosis is highly dependent on collagens aggregation in target organ. But, no one reported the relationship between DDR1 shedding and liver fibrosis. Methods: Here, we valuated the N-Terminal DDR1 in cell culture suspension, which treated by collagen I. We also contributed DDR1 shedding in (Bible- Duct Ligation) BDL mouse model, CCL4 induced liver fibrosis mouse model, HBV related liver fibrosis mouse model, and checked the serum N-terminal DDR1 by Elisa Assay. Furthermore, clinical blood specimens from patients with different stage of liver fibrosis were measured by DDR1-N terminal antibody using Elisa Assay. Results: We found that shedding is not a result of DDR1 signaling, but it results from collagen binding to the ecto- domain of DDR1. More collagen added in culture cell, more N-terminal DDR1 could be detected in suspension. The worse fibrosis of liver in all three mouse models, the more DDR1 shedding was diagnosed. Furthermore, the worse fibrosis of patients, the more N- teminal DDR1 was checked out in their serum. Conclusion: In this report, we identified DDR1 shedding could secret N-teminal DDR1 in serum, which is induced by collagen binding. N- teminal DDR1 was supposed to be a diagnostic hall marker of liver fibrosis.