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  • Title: Differential expression of matrix-metalloproteinase-1 and -2 genes in normal and fibrotic human liver.
    Author: Milani S, Herbst H, Schuppan D, Grappone C, Pellegrini G, Pinzani M, Casini A, Calabró A, Ciancio G, Stefanini F.
    Journal: Am J Pathol; 1994 Mar; 144(3):528-37. PubMed ID: 8129038.
    Abstract:
    Altered degradation of extracellular matrix has been implicated in the pathogenesis of hepatic fibrosis. We investigated levels and cellular sites of gene expression of two major collagen-degrading enzymes, matrix-metalloproteinase (MMP)-1 (fibroblast type-interstitial collagenase) and MMP-2 (72-kd gelatinase, type IV collagenase) in five normal and 18 fibrotic human livers as well as in cultured human hepatic fat-storing cells by Northern blot analysis and in situ hybridization. Fat-storing cells expressed both MMP-1 and MMP-2 RNA in vitro. In vivo, MMP-1 was undetectable in mesenchymal and parenchymal cells of all liver specimens, whereas MMP-2 transcripts were expressed in all livers by vimentin-positive, CD68-negative mesenchymal cells. Mesenchymal cells of all fibrotic livers displayed high transcript levels of transforming growth factor-beta 1, which is known to modulate MMP expression. Along with de novo fibrogenesis and possibly influenced by transforming growth factor-beta 1, expression of MMP-2 in the absence of MMP-1 expression may be responsible for the quantitative and qualitative changes of extracellular matrix observed in chronic liver disease.
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