Human liver fibroblast capacity for synthesizing interstitial collagenase in vitro

si e s------------------------ABSTRACT------------------------- P4 initiates specifically the degradation of interstitial collagen types I-III. This enzyme is thus directly involved in the remodeling of the connective matrix. Fibroblasts are considered as the major source of interstitial collagenase in many tissues. However previous studies shown that liver fibroblasts did not spontaneously produce the enzyme. We have thus measured the steady-state levels of mRNA for interstitial procollagenase and quantified interstitial collagenase activity in cultured human liver fibroblasts, in presence or not of interleukin-1 or tumor necrosis factor. We demonstrate that human liver fibroblasts have the capacity for producing interstitial collagenase and that this production is regulated at a transcriptional step. We suggest that the liver fibroblast could represent a key cell for therapeutic strategies of fibrosis reversal.