In liver fibrosis and cirrhosis there is a change in both the Liver fibrosis results from a relative imbalance beamount and relative composition of the hepatic extracellular tween synthesis and degradation of matrix proteins. We matrix. 1 Current evidence suggests that hepatic stellate cells have previously described release of the potent collagen-(lipocytes, fat-storing or Ito cells) are central to this process ase inhibitor, tissue inhibitor of metalloproteinase-1 both as the major source of fibrillar and nonfibrillar matrix (TIMP-1), by culture-activated human hepatic stellate proteins and matrix degrading metalloproteinases. 1-11 cells (HSCs). In this study, we have investigated the relaWe have previously shown that cultured hepatic stellate tive expression of TIMP-1 and interstitial collagenase in cells (HSCs) activated to a myofibroblastic phenotype express culture-activated rat HSCs and rat models of liver injury gelatinase A (72-kd type IV collagenase/gelatinase) 12,13 and and fibrosis. The complementary DNA (cDNA) for rat there is evidence to suggest that they also secrete stromely-TIMP-1 was obtained by homology polymerase chain reaction (PCR) and sequenced. By Northern analysis using sin. 14 A further metalloproteinase, interstitial collagenase, this probe, TIMP-1 messenger RNA (mRNA) expression expressed by mesenchymal and other cell types has degradawas up-regulated with HSC activation by culture on tive activity against native collagen types I and III, 15,16 explastic as defined by cellular expression of procollagen-pression of which could potentially initiate remodelling of 1. Interstitial collagenase mRNA was expressed in early fibrotic liver. culture (õ4 days) but became undetectable in more actiInterstitial collagenase expression in liver has been varivated cells (7-21 days). By activity assay of serum-free ously ascribed to parenchymal and sinusoidal liver cells, incell-conditioned media, TIMP-1 was found to be released cluding Kupffer cells 17,18 and hepatocytes. 19,20 There is also in increasing concentrations with duration of culture on some evidence to indicate that HSCs are a cellular source of plastic. Expression of TIMP-1, interstitial collagenase, interstitial collagenase in liver; studies on a passaged celland procollagen-1 mRNAs were studied in rat models of line derived by outgrowth from human liver (of possible HSC biliary and parenchymal injury (bile duct ligation and origin) showed that interstitial collagenase is expressed conCCl 4 administration) by ribonuclease protection assay. stitutively and is up-regulated in response to interleukin-TIMP-1 mRNA expression was increased at 6, 24 hours, 1 and tumor necrosis factor a. 21 Li et al. have also shown and 3 days after bile duct ligation and was also shown collagenase activity in cultured rat HSCs which was into rise in acute CCl 4 liver injury and remain elevated as creased in response to polyunsaturated lecithin. 22 the liver became fibrotic. TIMP-1 expression precededIn studies undertaken to measure interstitial collagenase proc...