HUMAN MYOFIBROBLASTLIKE CELLS OBTAINED BY OUTGROWTH ARE REPRESENTATIVE OF THE FIBROGENIC CELLS IN THE LIVER

During human fibrogenesis, myofibroblastlike cells proliferate and are the main source of fibrosis components. We have used cultured myofibr oblastlike cells obtained by outgrowth from explants of human liver to study the expression of extracellular matrix (ECM) components and mat rix-metalloproteinase-2 (MMP-2). These cells contained types I, III, I V, and V procollagen messenger RNAs (mRNAs). They also expressed mRNAs for laminin B1 chain and for cellular and plasma fibronectin. The cor responding proteins were detected by immuno-cytochemistry. MMP-2 expre ssion was shown by Northern blot and gelatin zymography. Because trans forming growth factor beta 1 (TGF beta 1) is considered an important m ediator in liver fibrogenesis, we examined its effect on expression of ECM components by cultured human myofibroblastlike cells. TGF beta 1 increased collagen mRNAs steady-state levels and total collagen secret ion in the culture medium. It also increased fibronectin mRNA levels b ut had no effect on laminin mRNA or (MMP-2 expression. In summary, cul tured human myofibroblastlike cells express those ECM components that accumulate during hepatic fibrogenesis, indicating the usefulness of t his model to study mechanisms of human liver fibrogenesis, In addition to the mitogenic effect of TGF beta 1 on human myofibroblastike cells , we now demonstrate its stimulation of ECM accumulation in these cell s, thus emphasizing the central role of TGF beta 1 and myofibroblastli ke cells in the pathophysiology of human hepatic fibrosis.