Kinetics of MMP-1 and MMP-3 produced by mast cells and macrophages in liver fibrogenesis of rat

Background: The involvement of whether macrophages and mast cells in the kinetics of matrix metalloproteinases-1 (MMP-1), MMP-3 and MMP-9, tissue inhibitors of metalloproteinases-1 (TIMP-1) and TIMP-2 in hepatic fibrosis/cirrhosis was examined. Materials and Methods: The MMPs and TIMPs were examined by histopathology, immunohistochemistry and immunoblotting using carbon tetrachloride-induced fibrotic rat liver. Results: MMP-1 increased in proportion to the development of fibrosis and reached maximum at week 14. In the first four weeks, MMP-3 expression was mainly observed in many hepatocytes. At week 8, the macrophages in the fibrous septa, as well as hepatocytes, expressed MMP-3. TIMP-1 and -2 progressively increased throughout the experimental periods. The MMP-1 expression in the mast cells, however, did not decrease the degree of liver cirrhosis. Conclusion: MMP-1, TIMP-1 and -2 expressions increased in the late stages of fibrosis and cirrhosis. During recovery, the MMP-3 expression of macrophages greatly increased in the unresolved fibrous septa.