Expression and activation of pro-MMP-2 and pro-MMP-9 during rat liver regeneration

Partial hepatectomy triggers a variety of biological phenomena, which culmi nate in regeneration of the liver mass. Hepatocyte proliferation is a major feature of the regenerating liver after partial hepatectomy. Previous stud ies in our laboratory suggested that hepatic matrix remodeling might be a p rerequisite process for hepatocyte proliferation in the regenerating liver. In the present study we use immunohistochemical staining, Western blot ana lysis, and gelatin zymography to show that the inactive matrix metalloprote inases (MMPs), pro-MMP-2 and pro-MMP-9, are elevated at 30 minutes and acti vated at 6 to 12 hours and at 3 to 6 hours, respectively, after hepatectomy Sham-operated livers did not show an increase in inactive pro-MMP-2 and pr o-MMP-9 and did not contain active MMP-2 or MMP-9. To examine whether tissu e inhibitor of matrix metalloproteinase-1 (TIMP-1) is changed to regulate t he activities of MMPs after partial hepatectomy, the level of TIMP-1 protei n was analyzed by both immunohistochemistry and Western blot analysis. The level of TIMP-1 protein appears to increase by 6 to 18 hours, implying that an increase in TIMP-1 regulates activities of active MMP-2 and MMP-9, Take n together, these results suggest that hepatic matrix remodeling is mediate d by activated MMPs, which contribute to modulation of the environment surr ounding hepatocytes during rat liver regeneration.