In vitro migratory potential of rat quiescent hepatic stellate cells and its augmentation by cell activation

In liver injury, hepatic stellate cells are considered to depart from the s inusoidal wall and accumulate in the necrotic lesion through migration and proliferation. In this study, we investigated the migratory capacity of qui escent stellate cells in vitro and analyzed the relationship with prolifera tive response. Freshly isolated stellate cells that were seeded in the uppe r chamber of Cell Culture Insert (Becton Dickenson, Franklin Lakes, NJ) sta rted to migrate to the lower chamber at 1 day and increased in migration in dex to 19% at 2 days, Cells in the lower chamber were stretched in shape wi th many lipid droplets and showed quiescent properties, i.e., negative expr ession of alpha-smooth muscle actin (alpha-SMA) or platelet-derived growth factor receptor-beta (PDGFR-beta). Migratory capacity in quiescent cells wa s also shown in the Matrigel-coated insert. Matrix metalloproteinase-2 (MMP -2) messenger RNA expression was low just after isolation, but was enhanced as migration became prominent. Migrating cells further showed higher proli ferative activity than resting ones. The presence of PDGF/BB and Kupffer ce lls accelerated stellate cell migration by the chemotactic mechanism and co ncurrently augmented proliferation, whereas that of dexamethasone and inter feron-gamma (IFN-gamma) attenuated migration as a result of general suppres sion effects. Compared with quiescent ones, alpha-SMA and PDGFR-beta-positi ve activated stellate cells obtained by 14-day culture exhibited more rapid and prominent migration, being regulated by mediators in a similar manner as described previously. These data indicate that quiescent stellate cells undergo migration, which is Linked to proliferation and enhanced by PDGF/BB and Kupffer cells, suggesting the involvement of this function in the init ial phase of development of postnecrotic fibrosis.