Differential expression of matrix-metalloproteinase-1 and -2 genes in normal and fibrotic human liver

Am J Pathol. 1994 Mar;144(3):528-37.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoradiography
  • Blotting, Northern
  • Cells, Cultured
  • Collagenases / analysis*
  • Collagenases / genetics*
  • Collagenases / metabolism
  • Gelatinases / analysis*
  • Gelatinases / genetics*
  • Gelatinases / metabolism
  • Gene Expression Regulation, Enzymologic / genetics*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Liver / chemistry*
  • Liver / cytology
  • Liver / pathology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Matrix Metalloproteinase 1
  • Matrix Metalloproteinase 2
  • Metalloendopeptidases / analysis*
  • Metalloendopeptidases / genetics*
  • Metalloendopeptidases / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics


  • RNA, Messenger
  • Collagenases
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 1